Dysregulated relationship of inflammation and oxidative stress in major depression

Chronic inflammation and oxidative stress have been implicated in the pathophysiology of Major Depressive Disorder (MDD), as well as in a number of chronic medical conditions. The aim of this study was to examine the relationship between peripheral inflammatory and oxidative stress markers in un-medicated subjects with MDD compared to non-depressed healthy controls and compared to subjects with MDD after antidepressant treatment. We examined the relationships between IL-6, IL-10, and the IL-6/IL-10 inflammatory ratio vs. F2-isoprostanes (F2-IsoP), a marker of oxidative stress, in un-medicated MDD patients (n = 20) before and after 8 weeks of open-label sertraline treatment (n = 17), compared to healthy non-depressed controls (n = 20). Among the un-medicated MDD subjects, F2-IsoP concentrations were positively correlated with IL-6 concentrations (p < 0.05) and were negatively correlated with IL-10 concentrations (p < 0.01). Accordingly, F2-IsoP concentrations were positively correlated with the ratio of IL-6/IL-10 (p < 0.01). In contrast, in the control group, there were no significant correlations between F2-IsoPs and either cytokine or their ratio. After MDD subjects were treated with sertraline for 8 weeks, F2-IsoPs were no longer significantly correlated with IL-6, IL-10 or the IL-6/IL-10 ratio. These data suggest oxidative stress and inflammatory processes are positively associated in untreated MDD. Our findings are consistent with the hypothesis that the homeostatic buffering mechanisms regulating oxidation and inflammation in healthy individuals become dysregulated in untreated MDD, and may be improved with antidepressant treatment. These findings may help explain the increased risk of comorbid medical illnesses in MDD.     

Neuroanatomical differences between familial and sporadic schizophrenia and their parents: An optimized voxel-based morphometry study

Symptomatic differences have been reported between patients with familial and sporadic schizophrenia. The present study examined neuroanatomical differences between the two subgroups and their parents using voxel-based morphometry. High-resolution T1-weighted images were obtained using 3 Tesla magnetic resonance imaging from 20 patients with schizophrenia (familial subgroup, n = 10; sporadic subgroup, n = 10), 20 of their parents (familial subgroup, n = 10; sporadic subgroup, n = 10) and 20 healthy volunteers. Gray matter density (GMD) was compared between groups on a voxel-by-voxel basis. Compared with the sporadic patients, the familial patients had significantly reduced GMD in the thalamus bilaterally. Reduction of GMD in bilateral thalami was also found in familial parents in comparison with sporadic parents. Compared with controls, both familial and sporadic patients had lower GMD involving bilateral insula, right temporal lobe, right occipital lobe, left lenticular nucleus and right cerebellum. However, only familial patients showed lower GMD than controls in the right thalamus. Compared with controls, only familial parents showed lower GMD in the right insula extending to the right temporal lobe and the right parietal lobule. The present data suggest that familial schizophrenia is associated with more severe structural abnormalities than sporadic schizophrenia, especially in the thalamus.     

Association between serum brain-derived neurotrophic factor and plasma interleukin-6 in major depressive disorder with melancholic features

Inflammatory processes as well as attenuation of brain-derived neurotrophic factor (BDNF) availability are involved in the pathophysiology of major depressive disorder (MDD). Although it is generally presumed that these two systems interact negatively in the brain, preclinical and human in vitro studies have shown synergistic rather than antagonistic interactions in the periphery. We therefore examined the association between serum levels of BDNF and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in patients with MDD (n = 1070) and non-depressed controls (n = 379) from the Netherlands Study of Depression and Anxiety. We used multiple regression analyses with serum BDNF as the dependent variable and we specifically tested the presence of BDNF–cytokine associations in DSM-IV-assigned melancholic MDD patients, identified by the Inventory of Depressive Symptomatology. After adjustment for sociodemographics, sampling variability, lifestyle indicators, somatic diseases and medication use, BDNF levels were predicted by the interaction between MDD diagnosis and IL-6 (p-interaction = .006). Stratified analyses showed that BDNF levels are indeed positively associated with IL-6 levels in MDD patients (β = .07, p = .02), but not in non-depressed controls (β = −.07, p = .23). When further stratified for melancholic and non-melancholic MDD (p-interaction = .005), IL-6 emerged as a robust positive predictor of BDNF only in the melancholic sample (β = .21, p = .01), wherein serum BDNF levels were accordingly enhanced. Post-hoc exploratory analyses verified an accentuated positive association of BDNF levels with leucocyte counts in melancholia. No significant associations emerged between BDNF and TNF-α. Overall, our cross-sectional approach may have disclosed an allostatic, BDNF-inducing component of peripheral immunity and/or an immunotrophic function of peripheral BDNF. Both scenarios may warrant further exploration, as they could inform new research concepts towards immune-based antidepressive treatment strategies.     

Does unilateral insular resection disturb personality? A study with epileptic patients

The insula is now regarded as a potential site of epileptogenesis in drug-resistant epilepsy, and the advent of microsurgical techniques has allowed insular cortectomy to become a treatment of choice when the insular cortex is involved in the seizure focus. However, considering the evidence of an insular role in socio-emotional processing, it remains unknown whether these cortical resections disturb personality and social behavior as experienced in daily life. We examined such changes in a group of patients (n = 19) who underwent epilepsy surgery involving partial or complete resection of the insula, and compared them to a group of patients who underwent standard temporal lobe epilepsy (TLE) surgery (n = 19) as a lesion-control group. Participants were assessed on the Iowa Scales of Personality Change, filled by a close relative at least six months after surgery. While postoperative changes did not significantly differ between groups on any of the ISPC items, insular resections were associated with mild but significant increases in irritability, emotional lability, anxiety, and frugality postoperatively, which, apart from anxiety, were not significant among TLE patients. Our results are congruent with the idea that the insula contributes to emotion processing. To our knowledge, this study is the first to systematically assess personality changes in a consecutive sample of patients with insular resections.     

Improvements in emotion regulation following repetitive transcranial magnetic stimulation for generalized anxiety disorder

Generalized anxiety disorder (GAD) is characterized by emotion regulation difficulties, which are associated with abnormalities in neural circuits encompassing fronto-limbic regions including the dorsolateral prefrontal cortex (DLPFC). The aim of this study was to determine whether DLPFC neuromodulation improves emotion regulation in patients with GAD. This is a secondary analysis from a randomized-controlled trial comparing 30 sessions of low-frequency right-sided active (n = 13) versus sham (n = 12, sham coil) repetitive transcranial magnetic stimulation (rTMS) at the right DLPFC in patients with GAD. Results indicated statistically significant improvements in self-reported emotion regulation difficulties at posttreatment and 3-month follow-up in the active group only. Improvements were found primarily in the domains of goal-directed behaviors and impulse control and were significantly associated with a global clinician rating of improvement. These preliminary results support rTMS as a treatment for GAD and suggest improved emotion regulation as a possible mechanism of change.     

When ageing meets the blues: Are current antidepressants effective in depressed aged patients?

“I had to wait 110 years to become famous. I wanted to enjoy it as long as possible.”, Jeanne Louise Calment (1875–1997).This review summarizes current knowledge of the effects of antidepressant drugs in elderly patients (double-blind placebo (n = 27) or active comparator-controlled clinical trials (n = 21) indexed in Pubmed in depressed patients aged ≥60) and in aged mice (≥9 months) and middle-aged rats (≥14 months) on depression-related symptoms and cognitive performances. Finally, other potential therapeutic targets for treating depression-related disorders in elderly patients are also addressed (neurogenesis, GABA_B receptor, 5-HT₄ receptor, mTOR signaling). Overall, the very few published preclinical studies (n = 12 in total) in middle-aged and aged rodents seem to suggest that selective serotonin reuptake inhibitors (SSRIs) may be less effective than tricyclic antidepressant drugs (TCAs) in ameliorating depression-like behavior and cognitive functions. On the other hand, results from clinical trials suggest that there is not a marked difference in efficacy and safety profiles of current marketed classes of antidepressant drugs.     

Omega-3/omega-6 fatty acid ratios in different phospholipid classes and depressive symptoms in coronary artery disease patients

Depressive symptoms are highly incident among coronary artery disease (CAD) patients and increase mortality. Reduced ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (omega-3 fatty acids) to arachidonic acid (AA, omega-6 fatty acid) concentrations have been linked with depressive symptoms in CAD. It remains unclear whether depressive symptoms are differentially associated with that ratio in different phospholipid classes, and this may have mechanistic implications. This study investigated associations between depressive symptoms in CAD patients and the EPA + DHA to AA ratio in the major phospholipid classes. This was a cross-sectional study of stable CAD patients. Sociodemographic, medical, medication, and cardiopulmonary fitness data were collected from each patient. Each patient was assessed for depressive symptoms using the 17-item Hamilton Depression Rating Scale (HAM-D). The percentage of EPA, DHA, and AA in each erythrocyte phospholipid class was determined using gas chromatography from fasting blood. Relationships between EPA + DHA to AA ratios and depressive symptoms were assessed using linear regression and were corrected for multiple comparisons. Seventy-six CAD patients were included (age = 61.9 ± 8.5, 74% male, HAM-D = 7.2 ± 5.9). In a backward elimination linear regression model, lower EPA + DHA to AA in erythrocyte phosphatidylinositol (B = −12.71, β = −0.33, p < .01) and sphingomyelin (B = −2.52, β = −0.37, p < .01) was associated with greater depressive symptom severity, independently of other known predictors. Other phospholipid classes were not associated with depressive symptoms. In conclusion, the relationship between EPA + DHA to AA ratios and depressive symptoms in CAD may not be consistent across phospholipid classes. Continued investigation of these potentially differential relationships may clarify underlying disease mechanisms.     

Interictal mood disorder and quality of life in active epilepsy

Although it is known that depressive symptoms have significant impact on quality of life (QOL) in epilepsy and that atypical symptoms are common in interictal depression, less is known about the clinical significance of the atypical form of interictal depression as opposed to major depressive disorder (MDD). We compared quality of life among 30 patients with epilepsy (1) with major depressive disorder (group D), (2) with interictal dysphoric disorder (group ID), and (3) without MDD or IDD (group ND). The mean t scores on the 31-item Quality of Life in Epilepsy questionnaire were lower in groups D (20.3, 95% CI 9.02–31.7, n = 3) and ID (38.7, 95% CI 34.2–43.2, n = 19) compared with group ND (59.1, 95% CI 52.2–66.1, n = 8). These results underscore the clinical significance of IDD that not only accounts for a large portion of mood symptoms in the population with epilepsy, but also is not adequately captured by the DSM-IV criteria for MDD [1].     

Disorder-specific versus transdiagnostic and clinician-guided versus self-guided treatment for major depressive disorder and comorbid anxiety disorders: A randomized controlled trial

Disorder-specific cognitive behavior therapy (DS-CBT) is effective at treating major depressive disorder (MDD) while transdiagnostic CBT (TD-CBT) addresses both principal and comorbid disorders by targeting underlying and common symptoms. The relative benefits of these two models of therapy have not been determined. Participants with MDD (n = 290) were randomly allocated to receive an internet delivered TD-CBT or DS-CBT intervention delivered in either clinician-guided (CG-CBT) or self-guided (SG-CBT) formats. Large reductions in symptoms of MDD (Cohen’s d ≥ 1.44; avg. reduction ≥ 45%) and moderate-to-large reductions in symptoms of comorbid generalised anxiety disorder (Cohen’s d ≥ 1.08; avg. reduction ≥ 43%), social anxiety disorder (Cohen’s d ≥ 0.65; avg. reduction ≥ 29%) and panic disorder (Cohen’s d ≥ 0.45; avg. reduction ≥ 31%) were found. No marked or consistent differences were observed across the four conditions, highlighting the efficacy of different forms of CBT at treating MDD and comorbid disorders.     

Characteristic brain hypoperfusion by 99mTc-ECD single photon emission computed tomography (SPECT) in patients with the first-episode schizophrenia

ObjectiveIn this study, we evaluated brain perfusion in patients with first-episode medicated schizophrenia using the new analytical method, statistical parametric mapping (SPM) applied to single photon emission computed tomography (SPECT).MethodWe performed SPECT with 99-Tc-ethyl cysteinate dimer (99mTc-ECD) of the brain and magnetic resonance imaging (MRI) in patients with schizophrenia (n = 30) and control subjects matched for age and gender (n = 37). A voxel-by-voxel group analysis was performed using SPM2 (Z > 3.0, P < 0.001, uncorrected for multiple comparisons).ResultIn comparison with control subjects, the volumes of the bilateral frontal areas were found to be decreased on MRI. Blood flow was found to be reduced in the bilateral temporal areas in the patients with schizophrenia on SPECT.ConclusionIn this study, patients with first-episode schizophrenia appeared to have significant bilateral temporal hypoperfusion, although temporal volumes were not significantly decreased in comparison with control subjects. Abnormality of temporal lobe blood flow in schizophrenia may show that functional changes occur earlier than structural changes, and may assist in the diagnosis of schizophrenia.     

Evaluation of periodontitis in hospital outpatients with major depressive disorder. A focus on gingival and circulating cytokines

An imbalance in stimulated cytokine production is associated with the etiopathogenesis of numerous diseases such as major depressive disorder (MDD) and periodontal disease. Increased cytokine levels have been reported in the gingival crevicular fluid (GCF) of patients with MDD. Thirty-six outpatients with MDD participated in this study. Each outpatient was age-matched (±3 years) with a healthy control (n = 36). The patients were controlled for race and smoking habits. Unstimulated and stimulated interleukin 6 (IL-6), interleukin 1β (IL-1β), and interferon-γ (INF-γ) production in whole blood culture (WBC) and IL-6 and IL-1β levels in the GCF were evaluated. Circulating levels of IL-6 and IL-1β (unstimulated) as well as GCF IL-1β were modestly lower in MDD patients, compared to the levels in age-matched controls (Mann–Whitney, p = 0.002, 0.0075, ANCOVA, p = 0.025, respectively). In the unstimulated group, there was no correlation between the levels of circulating IL-6 and GCF IL-6 (r = 0.07, p = 0.67), and between the levels of circulating IL-1β and the IL-1β level in the CGF (r = −0.08, p = 0.63). In the LPS stimulation group, there was no correlation between the levels of circulating levels of IL-6 and GCF IL-6 (r = 0. 02, p = 0.91) or between the circulating IL-1β and GCF IL-1β (r = 0.13, p = 0.42). We observed modest immunosuppression in MDD patients (evaluated by no stimulation whole blood culture [WBC]), especially in patients with melancholic depression, chronic depression, and severe depression.     

At the boundary of the self: The insular cortex in patients with childhood-onset schizophrenia,their healthy siblings,and normal volunteers

The insular cortex (insula), whose normal function involves delineating the boundary between self and non-self stimuli, has been implicated in the pathophysiology of the positive symptoms of schizophrenia, including hallucinations and delusions. Childhood-onset schizophrenia (COS), that includes the onset of psychosis before age 13, is a severe and continuous form of the illness which shows profound and global progressive cortical brain abnormalities during adolescence which merge in the adult pattern with age. Using prospectively acquired anatomic brain magnetic resonance imaging (MRI) scans, a matched sample of COS patients, their nonpsychotic full siblings and healthy volunteers, we measured insular volume using the FreeSurfer automated software. COS patients (n = 98; 234 scans) had significantly lower right (p = 0.003), left (p < 0.001), and total (p < 0.001) insular volumes than healthy volunteers (n = 100; 248 scans). Right insular volume negatively correlated with positive symptoms as measured by the Scale for the Assessment of Positive Symptoms (SAPS) (p = 0.02), while both left (p = 0.01) and right (p = 0.006) insula volumes were positively correlated with overall functioning, as measured by the Children's Global Assessment Scale (CGAS) scores. COS siblings (n = 71; 153 scans), on the other hand, did not differ significantly from normal volunteers suggesting that the insular deficits are more related to the illness state than a familial endophenotype. These results also highlight the salience of the insula in positive symptoms of schizophrenia perhaps resulting from the inability to discriminate between self from the non-self in COS. Further work to connect insular deficits to other neurocircuitries is warranted.     

Rostral anterior cingulate cortex theta current density and response to antidepressants and placebo in major depression

ObjectiveTo assess whether pretreatment theta current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC) differentiates responders from non-responders to antidepressant medication or placebo in a double-blinded study.MethodsPretreatment EEGs were collected from 72 subjects with Major Depressive Disorder (MDD) who participated in one of three placebo-controlled trials. Subjects were randomized to receive treatment with fluoxetine, venlafaxine, or placebo. Low-resolution brain electromagnetic tomography (LORETA) was used to assess theta current density in the rACC and mOFC.ResultsMedication responders showed elevated rACC and mOFC theta current density compared to medication non-responders (rACC: p = 0.042; mOFC: p = 0.039). There was no significant difference in either brain region between placebo responders and placebo non-responders.ConclusionsTheta current density in the rACC and mOFC may be useful as a biomarker for prediction of response to antidepressant medication.SignificanceThis is the first double-blinded treatment study to examine pretreatment rACC and mOFC theta current density in relation to antidepressant response and placebo response. Results support the potential clinical utility of this approach for predicting clinical outcome to antidepressant treatments in MDD.     

Multisystem resiliency moderates the major depression–Telomere length association: Findings from the Heart and Soul Study

Major depressive disorder (MDD) has been associated with reduced leukocyte telomere length (LTL). It is not known, however, whether psychosocial and behavioral protective factors moderate this association. In the current study, we examine whether multisystem resiliency – defined by healthy emotion regulation, strong social connections, and health behaviors (sleep and exercise) – predicts LTL and mitigates previously demonstrated associations between depression diagnosis and LTL. LTL was measured, using a quantitative PCR assay, in 954 patients with stable cardiovascular disease in the Heart and Soul Study. In a fully adjusted model, high multisystem resiliency predicted longer LTL (b = 80.00, SE = 27.17, p = .003), whereas each individual factor did not. Multisystem resiliency significantly moderated the MDD-LTL association (p = .02). Specifically, MDD was significantly related to LTL at 1 SD below the mean of multisystem resiliency (b = −142.86, SE = 56.46, p = .01), but not at 1 SD above the mean (b = 49.07, SE = 74.51, p = .51). This study suggests that MDD associations with biological outcomes should be examined within a psychosocial–behavioral context, because this context shapes the nature of the direct relationship. Further research should explore the cognitive, neural, and other physiological pathways through which multisystem resiliency may confer biological benefit.     

Facial emotion perception in patients with epilepsy: A systematic review with meta-analysis

Facial emotion perception is a fundamental social competency relying on a specialised, yet distributed, neural network. This review aimed to determine whether patients with epilepsy have facial emotion perception accuracy impairments overall, or for a subset of emotions (anger, disgust, happiness, sadness, fear, and surprise), and the relationship to epilepsy type, demographic/treatment variables, and brain organisation. Database searches used PRISMA guidelines with strict inclusion/exclusion criteria. Thirty included studies assessed patients with temporal lobe (TLE; n = 709), frontocentral (FCE; n = 22), and genetic generalised (GGE; n = 48) epilepsy. Large deficits emerged in patients with epilepsy compared to controls (n = 746; Hedges’ g = 0.908–1.076). Patients with TLE were significantly impaired on all emotions except surprise; patients with GGE were significantly impaired in anger, disgust, and fear perception. Meta-regression of patients with TLE revealed younger age at testing was associated with lower accuracy. This review provides evidence for marked global deficits of emotion perception in epilepsy, with differential emotion-specific impairment patterns in patients with TLE and GGE.     

Expressive inhibition in response to stress: Implications for emotional processing following trauma

Expressive inhibition – the willful restriction of expressed emotion – is documented in individuals reporting trauma-related distress, but its impact on global affective functioning remains unclear. Theoretical models propose that chronic activation of negative emotion and deliberate restriction of affect operate synergistically to produce trauma-related emotional deficits. The current project examined the impact of these factors on subjective experience and physiological activation following exposure to an analog trauma. University students (N = 192; M_age = 20, 57% female, 42% White/Non-Hispanic) viewed a graphic film depicting scenes of a televised suicide. Participants then viewed either a sadness- or humor-eliciting film under instructions to inhibit [n_sadness = 45, n_humor = 52] or naturally express emotion [n_sadness = 48, n_humor = 47]. Expressive inhibition was associated with restricted amusement specifically among participants viewing the humor film. Inhibition also produced attenuated sympathetic and parasympathetic recovery, irrespective of film assignment. Evidence of disruptions in emotional processing supports models identifying inhibition as a possible mechanism in post-trauma affect dysregulation.     

Social and occupational functioning impairment in patients in partial versus complete remission of a major depressive disorder episode. A six-month prospective epidemiological study

PurposeTo evaluate social and occupational functioning in patients in partial remission (PR) compared with patients in complete remission (CR) of a major depressive disorder (MDD) episode.Subjects and methodsThis is a six-month prospective study. PR was defined as a score more than 7 and less or equal to 15 in the Hamilton Depression Rating Scale, and CR as less or equal to 7. All patients had been on acute antidepressant treatment during the previous three months and no longer met criteria for MDD. Functioning was assessed by the Social and Occupational Functioning Assessment Scale (SOFAS).ResultsMean (S.D.) patient age was 50.5 (14.5) years (N = 292) and 77% were female. At baseline, partial remitters showed greater impairment in social and occupational functioning than complete remitters (62.8 [12.6] versus 80.4 [10.5], respectively; P < .0001). After six months, only 47% PR versus 77% CR reached normal functioning, and SOFAS ratings for PR were below normal range (76.2 [12.3] PR versus 84.6 [9.4] CR; P < .0001). PR reported three times more days absent from work due to sickness than CR (63 days versus 20 days; P < .001).ConclusionWe conclude that PR of an MDD episode is associated with significant functional impairment that persists even after nine months of antidepressant treatment. Our results underline the importance of treating the patient until achieving full remission.     

Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder

Reductions in gray matter volume of the medial prefrontal cortex (mPFC), especially the rostral and subgenual anterior cingulate cortex (rACC, sgACC) are a widely reported finding in major depressive disorder (MDD). Inflammatory mediators, which are elevated in a subgroup of patients with MDD, activate the kynurenine metabolic pathway and increase production of neuroactive metabolites such as kynurenic acid (KynA), 3-hydroxykynurenine (3HK) and quinolinic acid (QA) which influence neuroplasticity. It is not known whether the alterations in brain structure and function observed in major depressive disorders are due to the direct effect of inflammatory mediators or the effects of neurotoxic kynurenine metabolites. Here, using partial posterior predictive distribution mediation analysis, we tested whether the serum concentrations of kynurenine pathway metabolites mediated reductions in cortical thickness in mPFC regions in MDD. Further, we tested whether any association between C-reactive protein (CRP) and cortical thickness would be mediated by kynurenine pathway metabolites. Seventy-three unmedicated subjects who met DSM-IV-TR criteria for MDD and 91 healthy controls (HC) completed MRI scanning using a pulse sequence optimized for tissue contrast resolution. Automated cortical parcellation was performed using the PALS-B12 Brodmann area atlas as implemented in FreeSurfer in order to compare the cortical thickness and cortical area of six PFC regions: Brodmann areas (BA) 9, 10, 11, 24, 25, and 32. Serum concentrations of kynurenine pathway metabolites were determined by high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) detection, while high-sensitivity CRP concentration was measured immunoturbidimetrically. Compared with HCs, the MDD group showed a reduction in cortical thickness of the right BA24 (p < 0.01) and BA32 (p < 0.05) regions and MDD patients with a greater number of depressive episodes displayed thinner cortex in BA32 (p < 0.05). Consistent with our previous findings in an overlapping sample, the KynA/3HK ratio and the log KynA/QA were reduced in the MDD group relative to the HC group (p’s < 0.05) and symptoms of anhedonia were negatively correlated with log KynA/QA in the MDD group (p < 0.05). Both KynA/3HK and log KynA/QA at least partially mediated the relationship between diagnosis and cortical thickness of right BA32 (p’s < 0.05). CRP was inversely associated with BA32 thickness (p < 0.01) and KynA/3HK partially mediated the relationship between CRP and the thickness of right BA32 (p < 0.05). The results raise the possibility that the relative imbalance between KynA and neurotoxic kynurenine metabolites may partially explain the reductions in mPFC thickness observed in MDD, and further that these changes are more strongly linked to the putative effects of neuroactive kynurenine metabolites than those of inflammatory mediators.     

Traumatic and spontaneous carotid and vertebral artery dissection in a level 1 trauma center

This study aimed to compare traumatic and spontaneous carotid artery dissection (CAD) and vertebral artery dissection (VAD) with respect to age, pre-morbid risk factors, and site of dissection. Chart review was performed for 49 patients with CAD and VAD admitted to Westchester Medical Center, a level 1 trauma center, from 1999 to 2007. Presentation was categorized into traumatic (n = 28, 57%) or spontaneous dissection (n = 21, 43%). Pre-morbid risk factors were analyzed. Location of dissection was identified and categorized into four possible segments. Patients with spontaneous dissection were likely to be over the age of 50 years (p < 0.05), and had significantly higher proportions of coronary artery disease (33% compared to 7%, p < 0.05), hypertension (57% compared to 18%; p < 0.01), and hypercholesterolemia (29% compared to 0%; p < 0.01). Of the 49 patients, 42 had imaging studies available for segmental analysis. In both traumatic CAD and VAD, dissection at Segment III (corresponds with the first and second cervical vertebrae), was the most common site (37.5% and 50%, respectively, p < 0.05). In contrast, Segment I (origin of the vessel to the fifth cervical vertebrae) was the most common site for spontaneous CAD and VAD (55% and 77%, respectively, p < 0.05). This cross-sectional study suggests that etiology plays an important role in the location of dissection. Traumatic CAD and VAD occur most commonly in Segment III. Spontaneous CAD and VAD occur most commonly in Segment I and are associated with increasing age and premorbid cerebrovascular risk factors.     

Increased clinical and neurocognitive impairment in children with autism spectrum disorders and comorbid bipolar disorder

Bipolar (BD) symptomatology is prevalent in children with autism spectrum disorders (ASD) and may lead to increased impairment. The current study compared clinical and neurocognitive impairment in children (7–13 years) diagnosed with ASD (n = 55), BD (n = 34), ASD + BD (n = 23), and a non-clinical control group (n = 27). Relative to the ASD group, the ASD + BD group reported elevated rates of aggression and delinquency, behavioral disorders, depression, obsessive-compulsive disorder, and suicidal ideation, and poorer performance on the Stroop Color-Word Test. Future research might address how best to improve diagnostic assessment and adapt treatment to meet the needs of this uniquely impaired population.