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Showing papers in "World Journal of Biological Psychiatry in 2012"


Journal ArticleDOI
TL;DR: These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005 and provide evidence-based practice recommendations that are clinically and scientifically meaningful.
Abstract: These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A-F; Bandelow et al. 2008b, World J Biol Psychiatry 9:242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.

494 citations


Journal ArticleDOI
TL;DR: Future research on the cerebral cell-type specific distribution of kynurenine metabolites and their brain-regional concentration imbalances will be required to connect peripheral immune changes, the hypotheses of blood–brain barrier dysfunction and glial pathology with concepts of altered neurotransmission in schizophrenia and major depression.
Abstract: Objectives. Previous studies have suggested that the pathogenesis of schizophrenia and major depression involves an altered peripheral immune system. It is not clear, however, whether such changes are associated with corresponding neuroinflammatory responses and disturbances of neurotransmission. Methods. This paper reviews the current state of knowledge about the involvement of immune alterations in schizophrenia and major depression and a possible link to disturbances of glutamatergic transmission. Results. Inflammatory endogenous modulators of the NMDA receptor, the kynurenine pathway metabolites, are potential candidates for such a link. Studies of the blood and cerebrospinal fluid have suggested a schizophrenia-related upregulation of the NMDA receptor antagonist kynurenic acid in astrocytes, analogous to the ketamine psychosis model. Conversely, it has been proposed that there is depression-related microglial synthesis of the NMDA receptor agonist quinolinic acid, which is consistent with the observation that ketamine has therapeutic effects in major depression. Few publications have studied NMDA receptor modulating kynurenines in the brain, however. Conclusions. Future research on the cerebral cell-type specific distribution of kynurenine metabolites and their brain-regional concentration imbalances will be required to connect peripheral immune changes, the hypotheses of blood–brain barrier dysfunction and glial pathology with concepts of altered neurotransmission in schizophrenia and major depression. Read More: http://informahealthcare.com/doi/abs/10.3109/15622975.2011.583941

142 citations


Journal ArticleDOI
TL;DR: The association with the BDNF gene Val66Met polymorphism makes hippocampal volume a potential candidate for an endophenotype of disorders presenting with reduced hippocampal volumes.
Abstract: Objectives. Converging evidence suggests that the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects brain structure. Yet the majority of studies have shown no effect of this polymorphism on hippocampal volumes, perhaps due to small effect size. Methods. We performed a meta-analysis of studies investigating the association between Val66Met BDNF polymorphism and hippocampal volumes in healthy subjects by combining standardized differences between means (SDM) from individual studies using random effect models. Results. Data from 399 healthy subjects (255 Val-BDNF homozygotes and 144 carriers of at least one Met-BDNF allele) in seven studies were meta-analysed. Both the left and right hippocampi were significantly larger in Val-BDNF homozygotes than in carriers of at least one Met-BDNF allele (SDM = 0.41, 95% Confidence Interval = 0.20; 0.62, z = 3.86, P = 0.0001; SDM = 0.41; 95% Confidence Interval = 0.20; 0.61, z = 3.81, P = 0.0001, respectively), with no evidence of public...

110 citations


Journal ArticleDOI
TL;DR: Children with ADHD showed significantly lower estimated BI in right and left thalamus compared to healthy controls and serum ferritin and T2* values did not correlate significantly in most regions.
Abstract: Objective Brain iron deficiency has been supposed to be involved in the pathophysiology of ADHD Available studies assessing iron in ADHD are based on serum ferritin, a peripheral marker of iron s

108 citations


Journal ArticleDOI
TL;DR: The results show that BDNF levels decline with age in women, whereas in men levels remain stable, suggesting that they serve as molecular trait factors independent of lifestyle factors.
Abstract: OBJECTIVES: Brain-derived neurotrophic factor (BDNF) is involved in major depressive disorder and neurodegenerative diseases. Clinical studies, showing decreased serum BDNF levels, are difficult to interpret due to limited knowledge of potential confounders and mixed results for age and sex effects. We explored potential determinants of serum BDNF levels in a community sample of 1230 subjects. METHODS: Multiple linear regression analyses with serum BDNF level as the dependent variable were conducted to explore the effect of four categories of potential BDNF determinants (sampling characteristics, sociodemographic variables, lifestyle factors and somatic diseases) and of self-reported depressive symptoms (Beck's Depression Inventory (BDI). RESULTS: Our results show that BDNF levels decline with age in women, whereas in men levels remain stable. Moreover, after controlling for age and gender, the assays still showed lower serum BDNF levels with higher BDI sum scores. Effects remained significant after correction for two main confounders (time of sampling and smoking), suggesting that they serve as molecular trait factors independent of lifestyle factors. CONCLUSIONS: Given the age-sex interaction on serum BDNF levels and the known association between BDNF and gonadal hormones, research is warranted to delineate the effects of the latter interaction on the risk of psychiatric and neurodegenerative diseases.

108 citations


Journal ArticleDOI
TL;DR: Most likely, no single ADHD biomarker can be identified, however, the use of a combination of markers may help to reduce heterogeneity and to identify homogeneous subtypes of ADHD.
Abstract: Objective. Psychiatric “nosology” is largely based on clinical phenomenology using convention-based diagnostic systems not necessarily reflecting neurobiological pathomechanisms. While progress has been made regarding its molecular biology and neuropathology, the phenotypic characterization of ADHD has not improved. Thus, validated biomarkers, more directly linked to the underlying pathology, could constitute an objective measure for the condition. Method. The task force on biological markers of the World Federation of Societies of Biological Psychiatry (WFSBP) and the World Federation of ADHD commissioned this paper to develop a consensus report on potential biomarkers of ADHD. The criteria for biomarker-candidate evaluation were: (1) sensitivity > 80%, (2) specificity > 80%, (3) the candidate is reliable, reproducible, inexpensive, non-invasive, easy to use, and (4) confirmed by at least two independent studies in peer-reviewed journals conducted by qualified investigators. Results. No reliable ...

103 citations


Journal ArticleDOI
TL;DR: The remission rates differed significantly among the three treatment groups using a modified intention to treat analysis that excluded subjects who did not respond to electroconvulsive therapy (ECT) during the current episode.
Abstract: Objectives. High frequency left-sided (HFL) and low frequency right-sided (LFR) unilateral repetitive transcranial magnetic stimulation (rTMS) are efficacious in treatment-resistant major depression (TRD). Similar benefit has been suggested for sequential bilateral rTMS (LFR then HFL). There are few published reports on the efficacy of sequential bilateral rTMS compared to HFL and sham rTMS. Therefore, this study evaluated the efficacy of HFL and sequential bilateral rTMS compared to sham in TRD. Methods. Subjects between the ages of 18 and 85 were recruited from a tertiary care university hospital. Seventy-four subjects with TRD and a 17-item Hamilton Depression Rating Scale (HDRS) greater than 21 were randomized to receive unilateral, bilateral, or sham rTMS. The rates of remission were compared among the three treatment groups. Results. The remission rates differed significantly among the three treatment groups using a modified intention to treat analysis that excluded subjects who did not resp...

100 citations


Journal ArticleDOI
TL;DR: Findings suggest the possibility that alterations in gene expression, including upregulation of Ttr and downregulation of several other genes, including Htr2a, may be involved in antidepressant-like effect of SB.
Abstract: Objectives. Epigenetic mechanisms, such as changes in gene expression resulting from chromatin remodeling through histone acetylation, have been implicated in the pathophysiology of depression. However, the antidepressant-like effect of the histone deacetylase inhibitor sodium butyrate (SB) has been inconclusive. The aim of this study was to examine the antidepressant-like effect of SB and elucidate its molecular mechanisms. Methods. We examined the antidepressant-like effect of SB in a forced swim test (FST) and a tail suspension test (TST). Hippocampal gene expression analyses using DNA microarray and real-time PCR were undertaken. Western blotting and ChIP assay were undertaken to examine whether histone acetylation was associated with changes in gene expression by SB. Results. Repeated administration of SB significantly reduced immobility on the FST and the TST, and significantly altered the levels of mRNA for several genes; e.g., upregulation of transthyretin (Ttr) and downregulation of serot...

97 citations


Journal ArticleDOI
TL;DR: The hypothesis that patients with depression show less and later declines into lower EEG vigilance stages under resting conditions than healthy controls is confirmed, and the vigilance theory of affective disorders linking a hyperstable vigilance regulation to depression is supported.
Abstract: Objectives. This study tested the hypothesis that patients with depression show less and later declines into lower EEG vigilance stages (different global functional brain states) under resting conditions than healthy controls, as proposed by the vigilance theory of affective disorders. Methods. Thirty patients with Major Depressive Disorder (19 female; mean age: 37.2 years, SD: 12.6) without psychotropic medication and 30 carefully age- and sex-matched controls (19 female; mean age: 37.3 years, SD: 12.8) without past or present mental disorders underwent a 15-min resting EEG. EEG-vigilance regulation was determined with a computer-based vigilance classification algorithm (VIGALL, Vigilance Algorithm Leipzig), allowing a classification of vigilance stages A (with substages A1, A2 and A3), B (with substages B1 and B2/3) and C. Results. Depressive patients spent significantly more time in the highest EEG vigilance substage A1, and less time in substages A2, A3 and B2/3 than controls. In depressive pa...

96 citations


Journal ArticleDOI
TL;DR: Findings are consistent with dysfunction of antinociceptive systems in MOH, which is influenced by anxiety, and may be a neurobiological basis for dependence in a subgroup of MOH patients.
Abstract: Objectives. Medication-overuse headache (MOH) is associated with psychiatric comorbidities. Neurobiological similarities to substance dependence have been suggested. This study investigated grey matter changes, focussing on pain and reward systems. Methods. Using voxel-based morphometry, structural MRIs were compared between 29 patients with both, MOH and migraine, according to International Headache Society criteria, and healthy controls. The Migraine Disability Assessment (MIDAS) score was used. Anxiety and depression were screened for with the Hospital Anxiety and Depression Scale (HADS) and confirmed by a psychiatrist, using the Mini International Neuropsychiatric Interview. Results. Nineteen patients (66%) had a present or past psychiatric disorder, mainly affective (N = 11) and anxiety disorders (N = 8). In all patients a significant increase of grey matter volume (GMV) was found in the periaqueductal grey matter of the midbrain, which correlated positively with the MIDAS and the HADS-anxiet...

95 citations


Journal ArticleDOI
TL;DR: High risk individuals for depression have reduced volume of brain regions related to emotional processing in particular when they additionally suffered childhood abuse, indicating that genetic and environmental factors like early life adversity influence brain structure possibly via epigenetic mechanisms and thus structural anomalies may precede the onset of the illness.
Abstract: Objective. The interplay of genetic and early environmental factors is recognized as an important factor in the aetiology of major depressive disorder (MDD). The aim of the present study was to examine whether reduced volume of hippocampus and frontal brain regions involved in emotional regulation are already present in unaffected healthy individuals at genetic risk of suffering MDD and to investigate whether early life adversity is a relevant factor interacting with these reduced brain structures. Method. Twenty unaffected first-degree relatives of patients with MDD (FHP: family history positive) and 20 healthy controls (FHN: family history negative) underwent high-resolution magnetic resonance imaging. Manual tracing of hippocampal sub-regions and voxel-based morphometry was used to compare groups and find association to early life adversity. Results. FHP subjects with history of emotional abuse had significantly smaller left and right hippocampal heads. VBM also showed smaller dorsolateral prefrontal c...

Journal ArticleDOI
TL;DR: The findings suggest that in addition to local deficits in the left auditory cortex and disturbed fronto-temporal connectivity, the interhemispheric auditory pathway might be involved in the pathogenesis of AVH.
Abstract: Objectives Auditory verbal hallucinations (AVH) are among the most common symptoms in schizophrenia Earlier studies suggest changes in the structural connectivity of auditory areas involved in the pathophysiology of auditory hallucinations Combining diffusion tensor imaging (DTI) and fibre tractography provides a unique opportunity to visualize and quantify entire fibre bundles Methods Fibre tracts connecting homotopic auditory areas via the corpus callosum were identified with DTI in ten first episode paranoid schizophrenia patients and ten healthy controls Regions of interest were drawn manually, to guide tractography, and fractional anisotropy (FA) – a measure of fibre integrity – was calculated and averaged over the entire tract for each subject Results There was no difference in the FA of the interhemispheric auditory fibres between schizophrenic patients and healthy controls However, the subgroup of patients hearing conversing voices showed increased FA relative to patients without

Journal ArticleDOI
TL;DR: Bifrontal ECT is not more effective than BT or RUL ECT but may have modest short-term benefits for specific memory domains and BF ECT has potential advantages, but given longer experience with BT and RUL, bif prefrontal ECT requires better characterization.
Abstract: Objectives Our aim was to perform a meta-analysis of randomized controlled trials comparing efficacy and side effects of bifrontal (BF) ECT to bitemporal (BT) or unilateral (RUL) ECT in depression

Journal ArticleDOI
TL;DR: This study provides further support for a role of inflammation in the pathophysiology of suicidality and finds significantly lower levels of VEGF in the seven patients who upon a mean follow-up of 13 years were found to have completed suicide.
Abstract: Objectives. Immunological differences have previously been associated with depression and suicidal behaviour. Several cytokines have been identifi ed as potentially important in understanding the pathophysiology of mood disorders and suicidality. Here we aimed to identify new infl ammatory biomarkers for suicide prediction. Methods. Plasma concentrations of interleukin (IL) 1-a, IL1-b, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFNG), tumor necrosis factor-a (TNF-a), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) were measured in 58 suicide attempters with a high throughput automated biochip immunoassay system. Patients were evaluated using the Montgomery – A sberg Depression Rating Scale (MADRS) and the Suicide Intent Scale (SIS). All patients were followed up for cause of death. Results. We found signifi cantly lower levels of VEGF in the seven patients who upon a mean follow-up of 13 years were found to have completed suicide. VEGF also showed a trend for negative correlation with the planning subscale of SIS. A trend could be shown for lower IL-2 and for higher IFNG levels in suicide victims. Conclusions. Our study provides further support for a role of infl ammation in the pathophysiology of suicidality. VEGF may be related with suicide risk.

Journal ArticleDOI
TL;DR: The hypothesis of abnormal white matter microstructure of fronto-temporal cortical networks in ASD, which is associated with core symptoms of the disorder, is supported.
Abstract: Objectives. There is increasing evidence that many of the core behavioural impairments in autism spectrum disorders (ASD) emerge from disconnectivity of networks that are important for social communication. The present study aimed at investigating which specific fibre tracts are impaired in ASD and if possible alterations of white matter are associated with clinical symptomatology. Methods. Eighteen children with ASD and 18 carefully matched typically developing controls aged 6–12 years were examined using diffusion tensor imaging (DTI) and voxel-based morphometry (VBM). Fractional anisotropy (FA) values were correlated with symptom severity as indexed by the children's scores on the Autisms Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). Results. Decreased FA values were identified for the fornix (FO), the superior longitudinal fasciculus (SLF) the corpus callosum and the uncinate fasciculus (UF) in the ASD group compared to controls, with most prominen...

Journal ArticleDOI
TL;DR: This study is the first to document that latent toxoplasmosis reduces GM in schizophrenia but not in controls, and it is believed that latent T. gondii-negative patients and controls consisted only of 289 voxels in temporal regions.
Abstract: Objectives. To address the role of latent T. gondii infection in schizophrenia we studied the infl uence of latent toxoplasmosis on brain morphology. Methods. An optimized voxel-based morphometry of magnetic resonance imaging was analyzed by analysis of variance with diagnosis and seropositivity as factors in 44 schizophrenic patients (12 T. gondii positive) and 56 controls (13 T. gondii positive). Results. Grey matter (GM) volume was reduced in schizophrenia patients compared with controls in the cortical regions, hippocampus and in the caudate. In the schizophrenia sample we found a signifi cant reduction of GM volume in T. gondii positive comparing with T. gondii -negative patients bilaterally in the caudate, median cingulate, thalamus and occipital cortex and in the left cerebellar hemispheres. T. gondii -positive and -negative controls did not differ in any cluster. Among participants seropositive to T. gondii the reduction of GM in the schizophrenia subjects was located in the same regions when comparing the entire sample (11,660 over-threshold voxels ( P 0.05, FWR corrected). The differences between T. gondii -negative patients and controls consisted only of 289 voxels in temporal regions. Conclusions. Our study is the fi rst to document that latent toxoplasmosis reduces GM in schizophrenia but not in controls.

Journal ArticleDOI
TL;DR: Certain schizophrenic patients may benefit significantly from the use of ECT and combination with medication appears to be preferable over either treatment alone or combination particularly with clozapine.
Abstract: Objectives. Despite the fact that many studies have addressed the use of ECT in schizophrenia questions on clinical use remain poorly answered and clinical application is largely based on data originating from depressed patients. Methods. We review data on the use of ECT in schizophrenic patients drawn from original studies indicated by a Pubmed search and referenced in recent and older expert reviews with a specific focus on four issues: symptom response, technical application, continuation/maintenance ECT and combination with medication. Results. Catatonic patients are the most responsive. Positive symptoms such paranoid delusions and affective symptoms follow. There are indications that ECT may improve responsivity to medication. No particular technical features stand out in studies except lengthier courses, but not for catatonia. Combination with medication appears to be preferable over either treatment alone and effective combination particularly with clozapine is supported by data. Use of co...

Journal ArticleDOI
TL;DR: In this paper, the authors describe Obsessive-compulsive disorder (OCD) as a chronic, often severe, neuropsychiatric disorder leading to a dramatic impairment in interpersonal and occupational functions.
Abstract: Objectives. Obsessive-compulsive disorder (OCD) is a chronic, often severe, neuropsychiatric disorder leading to a dramatic impairment in interpersonal and occupational functions. rTMS has been tri...

Journal ArticleDOI
TL;DR: The present results suggest that there are distinct serum alterations that occur before clinical manifestation of schizophrenia and bipolar disorder, which could lead to development of diagnostic tests to help clinical psychiatrists identify and classify vulnerable patients early in the disease process.
Abstract: Objectives. To determine whether a molecular signature is present in blood of patients with psychiatric disorders before manifestation of symptoms. Methods. Multiplex immunoassay analyses were carr...

Journal ArticleDOI
TL;DR: This clinical trial demonstrated statistically significant and clinical relevant effects of MPH ER in adults with ADHD for several self- and investigator-rated ADHD psychopathology and also functional efficacy measures.
Abstract: Objectives . This trial was performed to test the effi cacy and safety of an extended-release formulation of methylphenidate (MPH ER). Methods . A total of 162 adults with ADHD according to DSM-IV were treated for 8 weeks with either two daily individually body weight-adjusted doses of MPH ER up to 1 mg/kg per day ( N 84) or placebo ( N 78). The primary effi cacy outcome was the Wender – Reimherr Adult Attention Defi cit Disorder Scale (WRAADDS) 8 weeks after randomization. Secondary effi cacy measures were the ADHD Diagnostic Checklist (ADHD-DC), the Conners Adult Attention Defi cit Disorder Scale (CAARS-S:L), the Clinical Global Impression (CGI) and the Sheehan Disability Scale (SDS). Results . At week 8 a signifi cantly higher decline of the total WRAADDS score was found in the MPH ER group as compared to the placebo group ( P 0.0003). The rates of responders were 50% in the MPH ER and 18% in the placebo group ( P 0.0001). Furthermore, similar effects were observed for the secondary effi cacy variable: ADHD-DC score ( P 0.004), CAARS-S:L score ( P 0.008) and the SDS score ( P 0.017). 50% of the MPH ER group and 24.4% of the placebo group were improved “ much ” or “ very much ” according to the CGI rating ( P 0.0001). MPH ER treatment was well tolerated. At week 2 also the mean heart rate was signifi cantly higher in the MPH ER group as compared to the placebo group ( P 0.01). No differences between the study groups were observed regarding mean blood pressure at any visit. Conclusions . This clinical trial demonstrated statistically signifi cant and clinical relevant effects of MPH ER in adults with ADHD for several self- and investigator-rated ADHD psychopathology and also functional effi cacy measures.

Journal ArticleDOI
TL;DR: Findings show that psychometric schizotypy in healthy individuals is associated with volume reductions in cortical areas known to be altered in schizophrenia, thereby providing neurobiological evidence of a continuum between schizotypesy and schizophrenia.
Abstract: Objectives. Schizophrenia is associated with replicable grey matter volume reductions in fronto-temporo-limbic and subcortical regions. Psychometric schizotypy refers to a set of behavioural traits and cognitions thought to represent the subclinical manifestation of schizophrenia in the general population. While there is evidence of a continuum between schizophrenia and schizotypy at phenotypic, genetic and cognitive levels, no previous study has observed grey matter volume reductions associated with increased psychometric schizotypy levels in healthy individuals. Such evidence would provide further support for a relationship between non-clinical schizophrenia-like traits in the general population and the full-blown clinical condition of schizophrenia. Methods. We used magnetic resonance imaging to investigate the relationship between psychometric schizotypy and brain structure in 55 clinically unaffected and unmedicated volunteers. We performed a voxel-based morphometry analysis of grey matter vo...

Journal ArticleDOI
TL;DR: Report practice in this sample appears largely consistent with recent evidence-based treatment guidelines, and patients with GAD have frequently been treated with benzodiazepines before referral to a psychiatrist.
Abstract: Objective. To gain insight into the experience and practice of psychiatrists in the pharmacological management of patients with generalized anxiety disorder (GAD). Methods. Multiple-choice questionnaire completed by 501 psychiatrists (representing a 45% response rate) from 18 countries, selected by pharmaceutical company representatives to attend a scientific meeting, through having an interest in anxiety disorders. Results. Use of screening tools, routine structured diagnostic interviews, and practice guidelines was infrequent. Over one-third of patients did not receive their initial psychiatric consultation within a month after referral. A total of 45% of patients had symptoms for 2 years or longer before being diagnosed and treated. Most patients had been treated with benzodiazepines before referral. 80% of respondents always or often prescribed selective serotonin reuptake inhibitors (SSRIs), 43% serotonin–norepinephrine reuptake inhibitors (SNRIs), or pregabalin (35%) as first-line treatments...

Journal ArticleDOI
TL;DR: The study shows that veterans with psychotic PTSD carried more Met alleles of the BDNF Val66Met than non-psychotic veterans with PTSD or veterans without PTSD, adding further support to the hypothesis that psychotic PTSD is a more severe subtype of PTSD.
Abstract: Objective: Psychotic symptoms frequently occur in veterans with combat-related posttraumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) plays a major role in neurodevelopment, neuro-regeneration, neurotransmission, learning, regulation of mood and stress responses. The Met allele of the functional polymorphism, BDNF Val66Met, is associated with psychotic disorders. This study intended to assess whether the Met allele is overrepresented in unrelated Caucasian male veterans with psychotic PTSD compared to veteran controls. Method: The BDNF Val66Met variants were genotyped in 576 veterans: 206 veterans without PTSD and 370 veterans with PTSD subdivided into groups with or without psychotic features. Results: Veterans with psychotic PTSD were more frequently carriers of one or two Met alleles of the BDNF Val66Met polymorphism than veterans with PTSD without psychotic features and veterans without PTSD. Conclusions: The study shows that veterans with psychotic PTSD carried more Met alleles of the BDNF Val66Met than non-psychotic veterans with PTSD or veterans without PTSD. The results might add further support to the hypothesis that psychotic PTSD is a more severe subtype of PTSD.

Journal ArticleDOI
TL;DR: The extent of volumetric differences in this study is remarkable and suggests that amygdala volumes might be a surrogate marker for the personality property of aggressiveness in healthy human beings.
Abstract: Objective. Several lines of evidence suggest an association between the amygdala and the modulation of aggressive behaviour. Previous morphometric brain imaging studies have focused on the role of ...

Journal ArticleDOI
TL;DR: Alleles associated with reduced anti-inflammatory cytokine function were associated with PSD, supporting the cytokine hypothesis in its etiology.
Abstract: Objectives. Inflammatory cytokines are implicated in the pathophysiology of both stroke and depression, and their production is influenced by the transcriptional activity of particular gene polymorphisms. We hypothesised that alleles related to higher pro-inflammatory and/or lower anti-inflammatory cytokine production would be associated with post-stroke depression (PSD). Methods. In 276 stroke cases, depression was diagnosed using DSM-IV, and classified into major PSD (N = 29), all (major plus minor) PSD (N = 77), and control (N = 199) groups. Genotyping for six pro-inflammatory polymorphisms (TNF-α –850C/T and –308G/A, IL-1β –511C/T and + 3953C/T, IL-6 –174G/C, and IL-8 –251T/A) and two anti-inflammatory polymorphisms (IL-4 + 33T/C and IL-10 –1082G/A) was conducted. Individual associations with PSD were estimated using logistic regression models. Total numbers of potential risk alleles were calculated for pro-inflammatory and anti-inflammatory cytokine genes and analysed against depression using...

Journal ArticleDOI
TL;DR: Seasonal factors, such as daily amount of sunshine and global radiation, influence serotonin-1A receptor binding in limbic brain regions of healthy human subjects, underline the importance of seasonal factors in the regulation of the serotonergic transmission.
Abstract: Objective. Climate, in particular sunshine, influences mood and energy levels, creating a positive upswing of mood on bright, sunny days and negative downswing in cold, dark winter seasons. Higher serotonin transporter availability in healthy human subjects in times of lesser light exposure and lower serotonin levels have been shown in winter. Methods. We examined the light-dependent variations in serotonin-1A receptor binding in limbic regions in 36 drug-naive healthy human subjects. Receptor binding was quantified using positron emission tomography and the radioligand [carbonyl-11C]WAY-100635. Binding potential values were related to the amount of individual exposure to sunlight (daily duration of sunshine) and global radiation (total light intensity). Results. We found a 20–30% lower serotonin-1A receptor binding in the group exposed to a lower amount of global light radiation. Partial correlation analysis revealed significant positive correlations between the regional postsynaptic serotonin-1A...

Journal ArticleDOI
TL;DR: It is suggested that, in addition to reduced prefrontal activation, failure of de-activation is an important functional imaging abnormality in mania, and its location in the medial prefrontal cortex implies default mode network dysfunction in the disorder.
Abstract: Objectives. Manic patients have been found to show reduced activation in the prefrontal cortex and other regions during performance of cognitive tasks. However, little is known about de-activations...

Journal ArticleDOI
TL;DR: The preliminary results suggest that three polymorphisms in DRD2 are associated with childhood aggression, and the relationship between the dopamine system and aggressive behaviour in children is explored.
Abstract: Excessive or deficient levels of extracellular dopamine have been hypothesized to contribute to a broad spectrum of mood, motor, and thought abnormalities, and dopaminergic system genes have been implicated in aggressive behaviour from animal and human studies. Objective. We examined selected members of the dopaminergic system genes for association with child aggression. Method. We analyzed polymorphisms in the dopamine transporter DAT1/SLC6A3, dopamine receptor DRD2, and DRD4 genes in our sample of pervasive childhood aggression consisting of 144 cases paired with 144 healthy controls, matched for sex and ethnicity. Results. Aggressive children were significantly more likely to have the at least one copy of the G allele for the DRD2 A-241G polymorphism (genotypic P=0.02; allelic P=0.01). The DRD2 rs1079598 CC genotype was overrepresented in aggressive children compared to controls (genotype P=0.04). The DRD2 TaqIA T allele (P=0.01) and the TT genotype (P=0.01) were also significantly overrepresen...

Journal ArticleDOI
TL;DR: The results mirror preclinical findings indicating that gender plays a role in the association between BDNF and anxiety and suggest that BDNF might play arole in the pathophysiology of anxiety in women.
Abstract: Objectives. Whereas animal models indicate that brain-derived neurotrophic factor (BDNF) plays a role in anxiety-related behaviour, little is known about BDNF in patients with an anxiety disorder. We tested the hypothesis that serum BDNF levels are low in patients with an anxiety disorder as compared to healthy controls. We further examined the associations of gender and some of the clinical characteristics of anxiety with BDNF levels. Methods. Serum BDNF levels were determined in 393 unmedicated, non-depressed patients with social anxiety disorder, panic disorder, agoraphobia, and generalised anxiety disorder (66.7% females) and in 382 healthy controls (62.0% females). Results. Overall, there were no differences in BDNF levels among patients and controls, regardless of type of anxiety disorder. Analyses stratified by gender revealed that female patients had lower levels of BDNF relative to female controls (P 1 anxiety disorder (P < 0...

Journal ArticleDOI
TL;DR: In this article, the authors found that patients with bipolar disorder exhibited a pattern of inefficient engagement within the ventral frontopolar prefrontal cortex with evidence of segregation along the medial-lateral dimension for reward and working memory processing, respectively.
Abstract: Objectives. Emotional dysregulation in bipolar disorder is thought to arise from dysfunction within prefrontal cortical regions involved in cognitive control coupled with increased or aberrant activation within regions engaged in emotional processing. The aim of this study was to determine the common and distinct patterns of functional brain abnormalities during reward and working memory processing in patients with bipolar disorder. Methods. Participants were 36 euthymic bipolar disorder patients and 37 healthy comparison subjects matched for age, sex and IQ. Functional magnetic resonance imaging (fMRI) was conducted during the Iowa Gambling Task (IGT) and the n-back working memory task. Results. During both tasks, patients with bipolar disorder demonstrated a pattern of inefficient engagement within the ventral frontopolar prefrontal cortex with evidence of segregation along the medial-lateral dimension for reward and working memory processing, respectively. Moreover, patients also showed greater activation in the anterior cingulate cortex during the Iowa Gambling Task and in the insula during the n-back task. Conclusions. Our data implicate ventral frontopolar dysfunction as a core abnormality underpinning bipolar disorder and confirm that overactivation in regions involved in emotional arousal is present even in tasks that do not typically engage emotional systems.