Is Response to OROS‐Methylphenidate Treatment Moderated by Treatment with Antidepressants or Psychiatric Comorbidity? A Secondary Analysis from a Large Randomized Double Blind Study of Adults with ADHD

Aims: The main aim of this post hoc analysis was to evaluate whether response to osmotic release oral system (OROS) methylphenidate (OROS‐MPH) was moderated by the concomitant use of antidepressants in attention‐deficit/hyperactivity disorder (ADHD) adults stabilized on these medicines for the treatment of depression or anxiety disorders, or a history of mood, anxiety, or substance use disorders. Methods: Two hundred and ninety‐six subjects were screened for participation; 227 were randomized (112 to OROS‐MPH and 115 to placebo), and 223 were analyzed (N= 109 and N= 114 for OROS‐MPH and placebo, respectively). Subjects with anxiety disorders and depression treated with a stable medication regimen of non‐MAOI antidepressants or benzodiazepines for at least 3 months could be enrolled in the study. Subjects currently receiving pharmacotherapy for anxiety disorders or depression were required to have Hamilton‐Depression and Hamilton‐Anxiety rating scales below 15 (mild range). Results: Concomitant antidepressant use at baseline was not associated with ADHD response, OROS‐MPH dose, study completion rate, adverse effects, or exacerbation of anxiety/depression. We did find nominally significant evidence that a lifetime history of mood (P= 0.09) or anxiety (P= 0.04) disorders was a moderator of ADHD symptoms and that a lifetime history of substance use disorder (P= 0.02) was a potential moderator of dose at endpoint. Discussion and Conclusions: We found few moderating effects in this large clinical trial of OROS‐MPH in adults with ADHD, which supports the robustness of the clinical response to OROS‐MPH in adult ADHD despite variable clinical pictures.     

Genetic and environmental influences on the co‐morbidity between depression,panic disorder,agoraphobia, and social phobia: a twin study

Background: Major depression (MD) and anxiety disorders such as panic disorder (PD), agoraphobia (AG), and social phobia (SP) are heritable and highly co‐morbid. However, the relative importance of genetic and environmental etiology of the covariation between these disorders, particularly the relationship between PD and AG, is less clear. Methods: This study measured MD, PD, and AG in a population sample of 5,440 twin pairs and 1,245 single twins, about 45% of whom were also scored for SP. Prevalences, within individual co‐morbidity and twin odds ratios for co‐morbidity, are reported. A behavioral genetic analysis of the four disorders using the classical twin design was conducted. Results: Odds ratios for MD, PD, AG, and SP in twins of individuals diagnosed with one of the four disorders were increased. Heritability estimates under a threshold‐liability model for MD, PD, AG, and SP respectively were .33 (CI: 0.30–0.42), .38 (CI: 0.24–0.55), .48 (CI: 0.37–0.65), and .39 (CI: 0.16–0.65), with no evidence for any variance explained by the common environment shared by twins. We find that a common genetic factor explains a moderate proportion of variance in these four disorders. The genetic correlation between PD and AG was .83. Conclusion: MD, PD, AG, and SP strongly co‐aggregate within families and common genetic factors explain a moderate proportion of variance in these four disorders. The high genetic correlation between PD and AG and the increased odds ratio for PD and AG in siblings of those with AG without PD suggests a common genetic etiology for PD and AG. Depression and Anxiety 26:1004–1011, 2009. Published 2009 Wiley‐Liss, Inc.     

Mental disorders in first-degree relatives of schizophrenics

A total 215 first-degree relatives of 88 twin probands with schizophrenia, mood disorders and nonaffective psychoses were studied. The twins' parents and siblings were personally interviewed with structured diagnostic instruments and diagnosed in accordance with DSM-III-R criteria. The first-degree relatives were interviewed by interviewers who were blind to the twins' diagnoses. Schizophrenia and schizotypal personality disorder were significantly more frequent in first-degree relatives of schizophrenic twins. Respectively, anxiety and mood disorders were significantly more prevalent among the parents and siblings of probands with mood disorders. Schizophrenic spectrum disorders were significantly more common in the families of schizophrenic probands compared with relatives of mood disorder probands, thus confirming a relationship between schizophrenia and schizophrenic spectrum disorders. However, we cannot, based on our study, specify whether this relationship is caused by genetic or environmental factors.     

Hippocampal morphology in lithium and non-lithium-treated bipolar I disorder patients, non-bipolar co-twins, and control twins

Background: Bipolar I disorder is a highly heritable psychiatric illness with undetermined predisposing genetic and environmental risk factors. We examined familial contributions to hippocampal morphology in bipolar disorder, using a population‐based twin cohort design. Methods: We acquired high‐resolution brain MRI scans from 18 adult patients with bipolar I disorder [BPI; mean age 45.6 ± 8.69 (SD); 10 lithium‐treated], 14 non‐bipolar co‐twins, and 32 demographically matched healthy comparison twins. We used three‐dimensional radial distance mapping techniques to visualize hippocampal shape differences between groups. Results: Lithium‐treated BPI patients had significantly larger global hippocampal volume compared to both healthy controls (9%) and non‐bipolar co‐twins (12%), and trend‐level larger volumes relative to non‐lithium‐treated BPI patients (8%). In contrast, hippocampal volumes in non‐lithium‐treated BPI patients did not differ from those of non‐bipolar co‐twins and control twins. 3D surface maps revealed thicker hippocampi in lithium‐treated BPI probands compared with control twins across the entire anterior‐to‐posterior extent of the cornu ammonis (CA1 and 2) regions, and the anterior part of the subiculum. Unexpectedly, co‐twins also showed significantly thicker hippocampi compared with control twins in regions that partially overlapped those showing effects in the lithium treated BPI probands. Conclusions: These findings suggest that regionally thickened hippocampi in bipolar I disorder may be partly due to familial factors and partly due to lithium‐induced neurotrophy, neurogenesis, or neuroprotection. Unlike schizophrenia, hippocampal alterations in co‐twins of bipolar I disorder probands are likely to manifest as subtle volume excess rather than deficit, perhaps indicating protective rather than risk effects. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Neurophysiological and genetic distinctions between pure and comorbid anxiety disorders

Anxiety disorders are often comorbid with major depression (MD) and alcohol use disorders (AUD). Two common functional polymorphisms in catechol-O-methyltransferase (COMT Val158Met) and brain-derived neurotrophic factor (BDNF Val66Met) genes have been implicated in the neurobiology of anxiety and depression. We hypothesized that attentional response and working memory (auditory P300 event-related potential and Weschler Adult Intelligence Scale, Revised digit symbol scores) as well as genetic vulnerability would differ between pure anxiety disorders and comorbid anxiety. Our study sample comprised 249 community-ascertained men and women with lifetime DSM-III-R diagnoses. We analyzed groups of participants with pure anxiety disorders, pure MD, pure AUD, comorbid anxiety, and no psychiatric disorder. Participants were well at the time of testing; state anxiety and depressed mood measures were at most only mildly elevated. Individuals with pure anxiety disorders had elevated P300 amplitudes (P=0.0004) and higher digit symbol scores (P<0.0001) compared with all the other groups. Individuals with comorbid anxiety had the greatest proportion of COMT Met158 and BDNF Met66 alleles (P=0.009) as well as higher harm avoidance-neuroticism (P<0.0005) than all other groups. Our results suggest that there may be two vulnerability factors for anxiety disorders with differing genetic susceptibility: (a) heightened attention and better working memory with mildly elevated anxiety-neuroticism, a constellation that may be protective against other psychopathology; and (b) poorer attention and working memory with greater anxiety-neuroticism, a constellation that may also increase vulnerability to AUD and MD. This refinement of the anxiety phenotype may have implications for therapeutic interventions.     

Anxiety and depression symptoms in psychometrically identified schizotypy

The neurodevelopmental vulnerability for schizophrenia appears to be expressed across a dynamic continuum of adjustment referred to as schizotypy. This model suggests that nonpsychotic schizotypic individuals should exhibit mild and transient forms of symptoms seen in full-blown schizophrenia. Given that depression and anxiety are reported to be comorbid with schizophrenia, the present study examined the relationship of psychometrically defined schizotypy with symptoms of depression and anxiety in a college student sample (n=1258). A series of confirmatory factor analyses indicated that a three-factor solution of positive schizotypy, negative schizotypy, and negative affect provided the best solution for self-report measures of schizotypy, anxiety, and depression. As hypothesized, the model indicated that symptoms of depression and anxiety are more strongly associated with the positive-symptom dimension of schizotypy than with the negative-symptom dimension. This is consistent with studies of schizophrenic patients and longitudinal findings that positive-symptom schizotypes are at risk for both mood and non-mood psychotic disorders, while negative-symptom schizotypes appear more specifically at risk for schizophrenia-spectrum disorders.     

抑郁症和精神分裂症共患焦虑障碍的研究

目的：了解抑郁症和精神分裂症患者与焦虑障碍的共病发生率及其相关因素。方法：对精神分裂症41例和抑郁症40例，用简明精神病评定量表(BPRS)、Hamilton抑郁量表(HAMD)、Hamilton焦虑量表(HAMA)、Liebowitz社交焦虑量表(LSAS)进行评定。结果：抑郁症与焦虑障碍的共病率为50．0％，精神分裂症与焦虑障碍的共病率为29．3％。LSAS与HAMA呈正相关(r=0．465)。有关抑郁症和精神分裂症患者共患焦虑障碍经多元逐步回归分析可排除药源性焦虑。结论：对抑郁症和精神分裂症共患焦虑障碍问题应引起高度重视。     

Association study between GABA receptor genes and anxiety spectrum disorders

Background : Human anxiety disorders are complex diseases with relatively unknown etiology. Dysfunction of the Gamma‐aminobutyric acid (GABA) system has been implicated in many neuropsychiatric conditions, including anxiety and depressive disorders. In this investigation, we explored four GABA receptor genes for their possible associations with genetic risk for anxiety disorders and depression.Methods : Our study sample consisted of 589 cases and 539 controls selected from a large population‐based twin registry based upon a latent genetic risk factor shared by several anxiety disorders, major depression, and neuroticism. We subjected these to a two‐stage protocol, in which all candidate genetic markers were screened for association in stage 1 (N=376), the positive results of which were tested for replication in stage 2 (N=752). We analyzed data from 26 single nucleotide polymorphisms (SNPs) from four GABA receptor genes: GABRA2, GABRA3, GABRA6, and GABRG2. Results : Of the 26 SNPs genotyped in stage 1, we identified two markers in GABRA3 that met the threshold (P≤.1) to be tested in stage 2. Phenotypic associations of these two markers failed to replicate in stage 2. Conclusions : These findings suggest that common variation in the GABRA2, GABRA3, GABRA6, and GABRG2 genes does not play a major role in liability to anxiety spectrum disorders. Depression and Anxiety 26:998–1003, 2009. Published 2009 Wiley‐Liss, Inc.     

The value of interleukin-12B (p40) gene promoter polymorphism in patients with schizophrenia in a region of East Turkey

Aims: It has been hypothesized that the activation of the immune system may be involved in the neuropathological changes occurring in the central nervous system of schizophrenic patients. Cytokines play a key role in the activation of the immune system. Moreover, they strongly influence the dopaminergic, noradrenergic and serotonergic neurotransmission. To the best of our knowledge, in schizophrenic patients, plasma levels of interleukin (IL)‐12 were investigated only in one study, where deregulation of IL‐12 was determined. However, genotypical variations of the IL‐12B (p40) gene have not been investigated for schizophrenic patients yet. Therefore, in the present study, we aimed to examine polymorphic variants of IL‐12B (p40) gene promoter region in patients with schizophrenia in a population of the Elazig Region of East Anatolia, Turkey. Methods: One hundred Turkish patients diagnosed with schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV), and 116 healthy control subjects participated in the present study. The genotype characteristics were determined by polymerase chain reaction‐based restriction fragment length polymorphism method using DNA extracted from peripheral blood. Results: Significant differences in both the genotype and allele frequencies were found between schizophrenia patients and control groups (P < 0.01). Conclusions: These findings may support the hypothesis that activation of the inflammatory response system and in particular, of Th‐1 cells, is involved in the pathophysiology of schizophrenia. We think that this study is the first trial associated with IL‐12 cytokine at the molecular genetic level on immune mechanisms for neuropsychiatric disorders including schizophrenia, and this perspective and the role of the cytokines in the pathogenesis of schizophrenia may constitute a reasonable target for the present and future treatment strategies and prognosis.     

Coagulation activation and fibrinolysis impairment are reduced in patients with anxiety and depression when medicated with serotonergic antidepressants

Aims: Anxiety disorders have been shown to be correlated with an activation of coagulation and impairment of fibrinolysis. The aim of the study was to assess whether medication with a serotonergic antidepressant, which has been associated with abnormal bleeding, may modify this effect. Methods: Thirty‐one anxiety patients, mostly with comorbid depression, and 31 healthy controls were included in the study. Group differences between anxiety patients medicated with a serotonergic antidepressant, patients without serotonergic antidepressant and controls were assessed for activated partial thromboplastin time, fibrinogen, factor VII, factor VIII, von Willebrand factor, von Willebrand ristocetin cofactor activity, prothrombin fragment 1 + 2, thrombin‐antithrombin complex, d ‐dimer, α2‐antiplasmin, plasmin‐α2‐antiplasmin complex (PAP), tissue plasminogen activator and plasminogen activator inhibitor. Intervening variables, such as age, sex, body mass index and smoking, were accounted for. Results: We found lower coagulation measures for fibrinogen (P = 0.03) and plasminogen activator inhibitor (P = 0.01), and higher levels of PAP (P = 0.046) in patients with serotonergic antidepressant than in patients without serotonergic antidepressant. When controlling for smoking and body mass index, differences between the two groups were significant for PAP (P = 0.02), von Willebrand ristocetin cofactor activity (P = 0.02) and activated partial thromboplastin time (P = 0.046). Coagulation scores were similar in patients with serotonergic antidepressant to those of healthy controls. Conclusions: Serotonergic antidepressants may counteract a procoagulant effect of anxiety and/or depression in anxiety patients.     

Twin concordance for DSM-III-R schizophrenia.

The monozygotic (MZ)/dizygotic (DZ) concordance rates for schizophrenia and the relationship between schizophrenia and schizophrenic spectrum disorders were studied in a sample of 31 MZ and 28 DZ schizophrenic probands and their co-twins. All subjects were personally interviewed with structured diagnostic instruments and classified according to DSM-III-R criteria. The concordance rates of 48% for MZ twins and 4% for DZ twins indicate a genetic transmission of DSM-III-R schizophrenia. In addition to the schizophrenic co-twins, 3 MZ co-twins had a noneffective psychotic disorder, thus supporting the hypothesis that genes are involved in the development of Axis I schizophrenic spectrum disorders. Schizotypal and paranoid personality disorders were observed in both MZ and DZ co-twins. These disorders may be familially related to schizophrenia, but a genetic relationship was not confirmed for the Axis II spectrum disorders. A substantial number of MZ co-twins of schizophrenic probands had no mental disorder.     

Genetic variation in D7S1875 repeat polymorphism of leptin gene is associated with increased risk for depression: a case‐control study from India

Background: Epidemiologic data suggest an association between obesity and depression, however findings vary considerably across different studies. Both depression and obesity are disabling disorders associated with loss over appetite control, influenced by genetic and environmental factors and are risk factors for diseases like hypertension, cardiovascular disorders, etc. This study attempts to establish a link between the symptoms of depression, metabolic disorders, and obesity, to unravel the underlying association/s. Methods: This exploratory case–control study comprises 133 clinically diagnosed depressed individuals and 136 age matched controls. DNA from all 269 subjects was genotyped for D7S1875 repeat polymorphism in the promoter region of Leptin (LEP) gene using polymerase chain reaction. Results: Frequency of the shorter allele of D7S1875 (<208 bp) was 0.73 in the depressive group versus 0.67 in the control group (P=.01). Cases homozygous for D7S1875≥208 bp alleles had significantly higher value of systolic (130 versus 122; P<.009) and diastolic (85.4 versus 81; P=.01) blood pressure (SBP and DBP) than the individuals homozygous for<208 bp allele. A similar trend was observed for SBP (127.8 versus 123.6; P=.03) among controls homozygous for the longer or the shorter allele. Thus, the LEP gene appears to be an important genetic determinant for susceptibility to depression in the Indian population (OR=1.4913, 95% CI=1.0334–2.1522; P=.04). Conclusions: Our findings suggest that LEP gene variants could be related to depression and associated co‐morbidities such as hypertension. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.     

Functional MRI correlates of visuospatial planning in out-patient depression and anxiety

van Tol MJ, van der Wee NJA, Demenescu LR, Nielen MMA, Aleman A, Renken R, van Buchem MA, Zitman FG, Veltman DJ. Functional MRI correlates of visuospatial planning in out‐patient depression and anxiety. Objective: Major depressive disorder (MDD) has been associated with executive dysfunction and related abnormal prefrontal activity, whereas the status of executive function (EF) in frequently co‐occurring anxiety disorders and in comorbid depression–anxiety is unclear. We aimed to study functional MRI correlates of (visuospatial) planning in MDD and anxiety disorders and to test for the effects of their comorbidity. Method: Functional MRI was employed during performance of a parametric Tower of London task in out‐patients with MDD (n = 65), MDD with comorbid anxiety (n = 82) or anxiety disorders without MDD (n = 64), and controls (n = 63). Results: Moderately/severely depressed patients with MDD showed increased left dorsolateral prefrontal activity as a function of task load, together with subtle slowing during task execution. In mildly depressed and remitted MDD patients, in anxiety patients, and in patients with comorbid depression–anxiety, task performance was normal and no activation differences were observed. Medication use and regional brain volume were not associated with altered visuospatial planning. Conclusion: Prefrontal hyperactivation during high planning demands is not a trait characteristic, but a state characteristic of MDD without comorbid anxiety, occurring independent of SSRI use. Disturbances in planning or the related activation are probably not a feature of anxiety disorders with or without comorbid MDD, supporting the current distinction between anxiety disorders and depression.     

Chernobyl exposure as stressor during pregnancy and behaviour in adolescent offspring

Objective: Research in animals has shown that exposure to stressors during pregnancy is associated with offspring behavioural disorders. We aimed to study the effect of in utero exposure to the Chernobyl disaster in 1986, and maternal anxiety presumably associated with that exposure, on behaviour disorder observed at age 14. Method: Exposed (n = 232) and non‐exposed Finnish twins (n = 572) were compared. A semi‐structured interview was used to assess lifetime symptoms of depression, generalized anxiety disorder, attention deficit hyperactivity disorder, conduct disorder and oppositional defiant disorder symptoms. Results: Adolescents who were exposed from the second trimester in pregnancy onwards, had a 2.32‐fold risk (95% CI: 1.13–4.72) of having lifetime depression symptoms, an increased risk of fulfilling DSM‐III‐R criteria of a major depressive disorder (OR = 2.48, 95% CI: 1.06–5.7), and a 2.01‐fold risk (95% CI: 1.14–3.52) of having attention deficit hyperactivity disorder symptoms. Conclusion: Perturbations in fetal brain development during the second trimester may be associated with the increased prevalence of depressive and attention deficit hyperactivity disorder symptoms.     

Serum cortisol and dehydroepiandrosterone-sulfate levels in schizophrenic patients and their first-degree relatives

Aims: Alterations in cortisol and dehydroepiandrosterone sulfate (DHEA‐S) levels are thought to play a role in the pathophysiology of neuropsychiatric disorders, including schizophrenia. The aim of this study was to investigate the role of serum cortisol and DHEA‐S in the pathophysiology of schizophrenia. Methods: Sixty schizophrenic patients, 70 healthy first‐degree relatives, and 60 healthy volunteers were included. Sociodemographic characteristics, data regarding disease duration and severity, as well as ongoing and previous drug use were recorded. Serum cortisol and DHEA‐S levels were measured. Results: Serum cortisol and DHEA‐S levels were significantly higher in the schizophrenia group compared with the first‐degree relatives and controls (P < 0.05). Serum cortisol levels in the first‐degree relatives were significantly higher than in the healthy controls (P < 0.05). There was no significant difference between the first‐degree relatives and healthycontrols in terms of DHEA‐S levels and between the three groups in terms of serum cortisol/DHEA‐S ratios. Conclusions: Elevated serum cortisol levels in schizophrenic patients might be associated with the role of cortisol in the pathophysiology of schizophrenia. Also, the elevation of serum cortisol levels in first‐degree relatives compared to controls suggests that similar pathophysiological processes might have a role in individuals without any disease symptoms, but with a genetic predisposition for schizophrenia. Elevated serum DHEA‐S levels might be the result of a compensatory response to elevated cortisol levels. Serum cortisol and DHEA‐S levels may be used as a biological marker for the diagnosis of schizophrenia; however, further studies with larger sample sizes are warranted to support this finding.     

Cognitive-behavioural therapy for late-life anxiety disorders: a systematic review and meta-analysis

Objective: To examine and estimate the efficacy of cognitive‐behavioural therapy (CBT) for late‐life anxiety disorders. Method: A systematic review and meta‐analysis of randomized controlled trials comparing CBT with i) a waiting‐list control condition and ii) an active control condition controlling for non‐specific effects in patients aged over 60 years and suffering from an anxiety disorder. The main outcome parameter of individual studies, i.e. effect on anxiety, was pooled using the standardized mean difference (SMD). Results: Seven papers fulfilled the inclusion criteria, including nine randomized controlled comparisons for 297 patients. Anxiety symptoms were significantly more reduced following CBT than after either a waiting‐list control condition [SMD = ?0.44 (95 CI: ?0.84 ?0.04), P = 0.03] or an active control condition [SMD = ?0.51 (95 CI: ?0.81, ?0.21), P<0.001]. Additionally, CBT significantly alleviated accompanying symptoms of worrying and depression. Conclusion: Cognitive‐behavioural therapy is efficacious for the treatment of late‐life anxiety disorders.     

A prospective latent analyses study of psychiatric comorbidity of DSM‐IV bipolar I and II disorders

Mantere O, Isometsä E, Ketokivi M, Kiviruusu O, Suominen K, Valtonen HM, Arvilommi P, Leppämäki S. A prospective latent analyses study of psychiatric comorbidity of DSM‐IV bipolar I and II disorders.
Bipolar Disord 2010: 12: 271–284. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objective: To test two hypotheses of psychiatric comorbidity in bipolar disorder (BD): (i) comorbid disorders are independent of BD course, or (ii) comorbid disorders associate with mood. Methods: In the Jorvi Bipolar Study (JoBS), 191 secondary‐care outpatients and inpatients with DSM‐IV bipolar I disorder (BD‐I) or bipolar II disorder (BD‐II) were evaluated with the Structured Clinical Interview for DSM‐IV Disorders, with psychotic screen, plus symptom scales, at intake and at 6 and 18 months. Three evaluations of comorbidity were available for 144 subjects (65 BD‐I, 79 BD‐II; 76.6% of 188 living patients). Structural equation modeling (SEM) was used to examine correlations between mood symptoms and comorbidity. A latent change model (LCM) was used to examine intraindividual changes across time in depressive and anxiety symptoms. Current mood was modeled in terms of current illness phase, Beck Depression Inventory (BDI), Young Mania Rating Scale, and Hamilton Depression Rating Scale; comorbidity in terms of categorical DSM‐IV anxiety disorder diagnosis, Beck Anxiety Inventory (BAI) score, and DSM‐IV‐based scales of substance use and eating disorders. Results: In the SEM, depression and anxiety exhibited strong cross‐sectional and autoregressive correlation; high levels of depression were associated with high concurrent anxiety, both persisting over time. Substance use disorders covaried with manic symptoms (r = 0.16–0.20, p < 0.05), and eating disorders with depressive symptoms (r = 0.15–0.32, p < 0.05). In the LCM, longitudinal intraindividual improvements in BDI were associated with similar BAI improvement (r = 0.42, p < 0.001). Conclusions: Depression and anxiety covary strongly cross‐sectionally and longitudinally in BD. Substance use disorders are moderately associated with manic symptoms, and eating disorders with depressive mood.     

Microvascular changes in late‐life schizophrenia and mood disorders: stereological assessment of capillary diameters in anterior cingulate cortex

L. Sinka, E. Kovari, M. Santos, F. R. Herrmann, G. Gold, P. R. Hof, C. Bouras and P. Giannakopoulos (2012) Neuropathology and Applied Neurobiology 38, 696–709 Microvascular changes in late‐life schizophrenia and mood disorders: stereological assessment of capillary diameters in anterior cingulate cortex Aims: Previous neuroimaging reports described morphological and functional abnormalities in anterior cingulate cortex (ACC) in schizophrenia and mood disorders. In earlier neuropathological studies, microvascular changes that could affect brain perfusion in these disorders have rarely been studied. Here, we analysed morphological parameters of capillaries in this area in elderly cases affected by these psychiatric disorders. Methods: We analysed microvessel diameters in the dorsal and subgenual parts of the ACC in eight patients with schizophrenia, 10 patients with sporadic bipolar disorder, eight patients with sporadic major depression, and seven age‐ and gender‐matched control cases on sections stained with modified Gallyas silver impregnation using a stereological counting approach. All individuals were drug‐naïve or had received psychotropic medication for less than 6 months, and had no history of substance abuse. Statistical analysis included Kruskal–Wallis group comparisons with Bonferroni correction as well as multivariate regression models. Results: Mean capillary diameter was significantly decreased in the dorsal and subgenual parts of areas 24 in bipolar and unipolar depression cases, both in layers III and V, whereas schizophrenia patients were comparable with controls. These differences persisted when controlling for age, local neuronal densities, and cortical thickness. In addition, cortical thickness was significantly smaller in both layers in schizophrenia patients. Conclusions: Our findings indicate that capillary diameters in bipolar and unipolar depression but not in schizophrenia are reduced in ACC. The significance of these findings is discussed in the light of the cytoarchitecture, brain metabolism and perfusion changes observed in ACC in mood disorders.     

Mood and anxiety disorders among rural,urban, and metropolitan residents in the United States

Objective: To estimate the correlates of mood and anxiety disorders among rural, urban and metropolitan residents in the United States. Methods: We analyzed the National Co-morbidity Survey (NCS), which yields the distribution and correlates of psychiatric disorders in a probability sample of U.S. population using DSM-III-R for diagnosis. Logistic regressions of mood and anxiety disorders were stratified by geographical area. Results: We found gender differences in mood disorders among urban (O.R. = 1.8, P < 0.0001) and metropolitan (O.R. = 1.6, P < 0.0001) but not among rural residents. Rural (O.R. = 0.2, P < 0.05) and urban (O.R. = 0.5, P < 0.05) African Americans were less likely to report mood disorders compared to rural and urban Whites. Similarly, we found gender differences in anxiety disorders among urban (O.R. = 2.0, P < 0.0001) and metropolitan (O.R. = 1.7, P < 0.0001), but not among rural residents. Conclusion: Rural men reported more mood and anxiety disorders than urban men, thus erasing expected rural gender differences in these disorders. Rural male mood and anxiety disorders may be a function of diminishing resources (steady, high paying jobs) or increasing financial strain particularly among Whites, who comprise a majority of rural residents.     

Factors associated with co‐morbid irritable bowel syndrome and chronic fatigue‐like symptoms in functional dyspepsia

Background It is unclear which factors explain the high co‐morbidity between functional dyspepsia (FD) and other functional somatic syndromes. The aim of this study is to investigate the association between gastric sensorimotor function, psychosocial factors and ‘somatization’ on the one hand, and co‐morbid irritable bowel syndrome (IBS) and chronic fatigue (CF)‐like symptoms on the other, in FD. Methods In 259 tertiary care FD patients, we studied gastric sensorimotor function with barostat (sensitivity, accommodation). We measured psychosocial factors (abuse history, alexithymia, trait anxiety, depression, panic disorder) and ‘somatization’ using self‐report questionnaires, and presence of IBS and CF‐like symptoms. Hierarchical multiple logistic regression was used to determine which of these factors were independently associated with co‐morbid IBS and CF‐like symptoms, including testing of potential mediator effects. Key Results Co‐morbid IBS or CF‐like symptoms respectively were found in 142 (56.8%) and 102 (39.4%) patients; both co‐morbidities were not significantly associated (P = 0.27). Gastric accommodation (β = 0.003, P = 0.04) and ‘somatization’ (β = 0.17, P = 0.0003) were independent risk factors for IBS (c = 0.74, P < 0.0001); the effect of adult abuse (β = 0.72, P = 0.20) was mediated by ‘somatization’. Depression (β = 0.16, P = 0.008) and ‘somatization’ (β = 0.18, P = 0.004) were overlapping risk factors for CF‐like symptoms (c = 0.83, P < 0.0001); the effects of alexithymia and lifetime abuse were mediated by depression and ‘somatization’, respectively. Conclusions & Inferences ‘Somatization’ is a common risk factor for co‐morbid IBS and CF‐like symptoms in FD and mediates the effect of abuse. Gastric sensorimotor function and depression are specific risk factors for co‐morbid IBS and CF‐like symptoms, respectively.