Comorbid AD Research Articles

Influence of affective disorders on outcomes after suboccipital decompression for adult Chiari I malformation

IntroductionAffective disorders (AD) have been shown to influence patient outcomes and healthcare resource utilization across several pathologies, though this relationship has not been described in patients with Chiari I malformations (CM-I). The aim of this study was to determine the impact of comorbid AD on postoperative events and healthcare resource utilization in adults following suboccipital decompression for CM-I. MethodsA retrospective study was performed using the 2016–2019 National Inpatient Sample database. Adults who underwent suboccipital decompression for CM-I were identified using ICD-10-CM codes. Patients were stratified into two cohorts, those with AD and those without (No AD). Patient demographics, comorbidities, operative characteristics, perioperative adverse events (AEs), and healthcare resource utilization were assessed. Multivariate logistic regression analyses were used to identify independent predictors of prolonged length of stay (LOS), exorbitant admission costs, and non-routine discharge (NRD). ResultsA total of 3985 patients were identified, of which 2780 (69.8%) were in the No AD cohort and 1205 (30.2%) were in the AD cohort. Patient demographics were similar, except for a greater proportion of Female patients than the No AD cohort (p = 0.004). Prevalence of some comorbidities varied between cohorts, including obesity (p = 0.030), ADHD (p < 0.001), GERD (p < 0.001), smoking (p < 0.001), and chronic pulmonary disease (p < 0.001). The AD cohort had a greater proportion of patients with 1–2 (p < 0.001) or ≥ 3 comorbidities (p < 0.001) compared to the No AD cohort. A greater proportion of patients in the AD cohort presented with headache compared to the No AD cohort (p = 0.003). Incidence of syringomyelia was greater in the No AD cohort (p = 0.002). A greater proportion of patients in the No AD cohort underwent duraplasty only (without cervical laminectomy) compared to the AD cohort (p = 0.021). Healthcare resource utilization was similar between cohorts, with no significant differences in mean LOS (No AD: 3.78 ± 3.51 days vs. 3.68 ± 2.71 days, p = 0.659), NRD (No AD: 3.8% vs. AD: 5.4%, p = 0.260), or mean admission costs (No AD: $20,254 ± 14,023 vs. AD: $29,897 ± 22,586, p = 0.284). On multivariate analysis, AD was not independently associated with extended LOS [OR (95%CI): 1.09 (0.72–1.65), p = 0.669], increased hospital costs [OR (95%CI): 0.98 (0.63–1.52), p = 0.930], or NRD [OR (95%CI): 1.39 (0.65–2.96), p = 0.302]. ConclusionOur study suggests that the presence of an AD may not have as much of an impact on postoperative events and healthcare resource utilization in adult patients undergoing Chiari decompression. Additional studies may be warranted to identify other potential implications that AD may have in other aspects of healthcare in this patient population.

Anti-Glycation, Anti-β-Amyloid Aggregation, and Antioxidant Effect of Cassia Seed-Derived Secondary Metabolites

Aggregation and non-enzymatic glycation of amyloidogenic peptides, amyloid-beta (Aβ), and insulin are key features of neuropathology. In this study, we evaluate the anti-glycation effect of Cassia seed-derived secondary metabolites on human insulin and bovine serum albumin, as well as their anti-Aβ aggregation and antioxidant effects using in vitro spectrofluorometric method, thioflavin T fluorescence, and peroxynitrite (ONOO‒) scavenging assay. Furthermore, molecular docking simulation was performed to investigate the binding characteristics of test compounds and Aβ42 peptide. Among 38 compounds, anthraquinones 9–12 and 14–18; naphthopyrones 24, 25, 27, and 33–36; and 38 from the naphthalenes and naphthalenic lactone groups showed moderate-to-good inhibition of AGE formation with IC50 values ranging from 7.52 ± 1.19 to 155.86 ± 0.79 µM. Likewise, compounds 5, 24, 15, 16, 27, and 20 showed good inhibition of D-ribose-mediated glycation of human insulin, with an IC50 value range of 46.37 ± 4.06 to 97.69 ± 7.88 µM. In the thioflavin-T assay, compounds 8 and 12 showed promising inhibition of Aβ aggregation, comparable to that of the reference compound morin. Molecular docking simulations confirmed that these active compounds have strong potential to interact with Aβ42 peptides and interrupt their self-assembly and conformational transformation, thereby inhibiting Aβ42 aggregation. In addition, compounds 5, 8, 10, 14, and 35 scavenged ONOO− at low concentrations. Overall, Cassia compounds’ anti-glycation, anti-Aβ aggregation, and antioxidant effects warrant further in vivo studies to evaluate their potential neuroprotective effects against comorbid AD and diabetes.

Decreased integrity of the monoaminergic tract is associated with a positive response to MPH in patients with vascular cognitive impairment - proof of principle study STREAM-VCI.

Patients with vascular cognitive impairment (VCI) are very heterogeneous in both symptoms and type of cerebrovascular pathology. This might be an important reason why there is no symptomatic treatment available for VCI patients. In this study, we investigated in patients with VCI, whether there was an association between a positive response to methylphenidate and galantamine and the type of cerebrovascular disease, structural damage to specific neurotransmitter systems, cerebral perfusion, and presence of co-morbid Alzheimer (AD) pathology. We included 27 VCI patients (mean age 67 years±8,30% female) from the STREAM-VCI trial who received placebo, methylphenidate(10mg), and galantamine(16mg) in a single challenge, cross-over design. In this study, we classified patients improving on a task for executive functioning after methylphenidate compared to placebo as methylphenidate responders (MPH+; resp. non-responders, MPH-) and patients improving on a task for memory after galantamine compared to placebo as galantamine responders (GAL+; resp. non-responders, GAL-). On baseline MRI, we visually assessed measures of cerebrovascular disease, automatically segmented white matter hyperintensities, used diffusion tensor imaging to visualize the integrity of monoaminergic and cholinergic neurotransmitter systems with mean diffusivity (MD) and fractional anisotropy (FA). Comorbid AD pathology was assessed using CSF or amyloid-PET. We tested differences between responders and non-responders using ANOVA, adjusting for age and sex. Nine patients were MPH+ vs 18 MPH-. MPH+ had higher MD (1.22±0.07 vs 0.94±0.05); p=.001) and lower FA (0.38±.01 vs 0.43±.01); p=.04) in the monoaminergic tract compared to MPH-. Eight patients were GAL+ and 18 GAL-. We found no differences between GAL+ and GAL- in any of the MRI measures. Information on co-morbid AD pathology was present in 17 patients. AD pathology tended to be more frequent in GAL+ vs GAL- (5(71%) vs 2(20%); p=.06). In patients with VCI, we found that decreased integrity of the monoaminergic tract is associated with a positive response to MPH. Responsiveness to galantamine may be related to co-morbid AD pathology.

Childhood atopic dermatitis is associated with cognitive dysfunction: A National Health Interview Survey study from 2008 to 2018

BackgroundAtopic dermatitis (AD) is a common inflammatory skin disease in children and adults. Little is known regarding the association of childhood AD with cognitive dysfunction. ObjectiveTo evaluate the association of AD and cognitive dysfunction, including memory impairment, developmental delays and attention deficit (hyperactivity) disorder in US children (age <18 years). MethodsData was analyzed from the National Health Interview Survey 2008 to 2018, which used a multistage, clustered, cross-sectional design. ResultsThe prevalences of cognitive dysfunction, such as memory impairment (0.87% vs 0.42%), developmental delays (6.96% vs 3.87%), and attention deficit (hyperactivity) disorder (10.78% vs 8.10%), were higher in children with vs without AD. In multivariable logistic regression models adjusting for age, sex, race, region, socioeconomic factors, allergic conditions, and mental health, childhood AD was associated with higher odds of memory impairment (adjusted odds ratio [95% confidence interval]: 1.84 [1.34-2.51]), developmental delays (1.54 [1.40-1.70]), and attention deficit (hyperactivity) disorder (1.31 [1.20-1.42]) compared with children without AD. Childhood atopic disease (defined as comorbid AD, asthma, allergic rhinitis, and food allergies) further increased the prevalence of developmental delays to 13.44% (2.10 [1.20-3.70]) in boys but not in girls. ConclusionIn a nationally representative sample of the US population, a statistically significant and positive association between childhood AD and atopic disease with cognitive dysfunction was identified (P < .001). Furthermore, a dimorphic relationship with developmental delays was identified between sexes.

Management of anxiety disorders in children with attention-deficit hyperactivity disorder: a narrative review.

Anxiety disorders are common comorbidities of attention deficit/hyperactivity disorder (ADHD) and conversely, ADHD is prevalent among anxious youths. A variety of treatments, both psychopharmacological and nonpsychopharmacological, are used to manage combined ADHD/anxiety disorder. This article aims to review the literature on the treatment of ADHD with comorbid anxiety disorders, and make evidence-based recommendations for clinical practice. In most cases, when ADHD is the primary condition, stimulants are the first-line of treatment, frequently resulting not only in improvement in ADHD symptoms but also alleviating the symptoms of the comorbid anxiety disorder. Stimulant treatment is relatively safe and well-tolerated in ADHD with comorbid anxiety disorder. When the stimulant administration does not attenuate the severity of the comorbid anxiety disorder, a treatment that targets specifically the anxiety disorder should be added. This recommendation, however, might be challenged by the impressive efficacy of atomoxetine for both the ADHD and anxiety disorder symptoms. Adjunctive cognitive-behavior therapy for anxiety disorder symptoms is strongly recommended and is considered superior to medication alone. Other options include adding pharmacological treatment for the anxiety symptoms. In moderate and severe cases of comorbid Ads, selective serotonin reuptake inhibitors can be added to the stimulants, with the required caution.

Abstract WP566: Vascular Regeneration Following Transient Hypertension by Perivascular Progenitor Cells and Abeta Clearance in a Transgenic Rat Model of Alzheimer’S Disease

The interplay between hypertension and amyloidogensis is understudied and lacks of preclinical model that captures both pathologies. Our therapeutic approach is designed to target the patients who present cerebrovascular injury in combination with AD pathology. We combined induced transient hypertension (via Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) in a transgenic rat model of AD that recapitulates Aβ peptide deposition and tau hyperphosphorylation in the adulthood followed by cognitive decline and neuronal loss in later life. We administered human umbilical cord perivascular cells (HUCPVC) to elicit brain vascular repair and scyllo-inositol (SI) to clear amyloid. Treatment outcomes were measured by perfusion MRI, immunohistochemistry (amyloid, tau hyperphosphorylation, vascular markers), and immunoblotting. Four weeks after the cessation of L-NAME, a single HUCPVC treatment was administered, and final imaging session conducted four weeks thereafter. Blood-flow was measured during both rest and CO 2 challenges at: baseline, immediately post-L-NAME, and at endpoint. L-NAME administration induced moderate hypertension in both TgAD-F344 and non-TgAD rats, manifested by increased systolic pressure, elevated plasminogen activator inhibitor-1, decreased vessel density and hippocampal resting perfusion reduction. Hippocampal hypoperfusion in the non-TgAD animals returned to baseline 4-weeks after cessation of L-NAME, whereas in TgAD-F344 rats it persisted until endpoint and was not rescued by HUCPVC+SI. Hippocampal vascular responsivity to hypercapnia increased twice as much in TgAD-F344 when compared to non-TgAD-F344 following L-NAME administration; it did not return to baseline levels 4-weeks after cessation of L-NAME in the vehicle-administered TgAD-F344 rats, whereas HUCPVC and HUCPVC+SI rescued hippocampal cerebrovascular hyperreactivity to baseline levels of TgAD-F344 rats. Transient hypertension caused sustained cerebrovascular dysfunction when associated with Aβ plaques, revealing an interaction between transient hypertension and AD pathology. Combinatorial treatment with SI and HUCPVC may be necessary to address cerebrovascular disease with comorbid AD.

Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression

ImportanceAlcohol dependence (AD) and major depression (MD) are leading causes of disability that often co-occur. Genetic epidemiologic data have shown that AD and MD share a common possible genetic cause. The molecular nature of this shared genetic basis is poorly understood.ObjectivesTo detect genetic risk variants for comorbid AD and MD and to determine whether polygenic risk alleles are shared with neuropsychiatric traits or subcortical brain volumes.Design, Setting, and ParticipantsThis genome-wide association study analyzed criterion counts of comorbid AD and MD in African American and European American data sets collected as part of the Yale-Penn study of the genetics of drug and alcohol dependence from February 14, 1999, to January 13, 2015. After excluding participants never exposed to alcohol or with missing information for any diagnostic criterion, genome-wide association studies were performed on 2 samples (the Yale-Penn 1 and Yale-Penn 2 samples) totaling 4653 African American participants and 3169 European American participants (analyzed separately). Tests were performed to determine whether polygenic risk scores derived from potentially related traits in European American participants could be used to estimate comorbid AD and MD. Main Outcomes and MeasuresComorbid criterion counts (ranging from 0 to 14) for AD (7 criteria) and MD (9 criteria, scaled to 7) as defined by the DSM-IV.ResultsOf the 7822 participants (3342 women and 4480 men; mean [SD] age, 40.1 [10.7] years), the median comorbid criterion count was 6.2 (interquartile range, 2.3-10.9). Under the linear regression model, rs139438618 at the semaphorin 3A (SEMA3A [OMIM 603961]) locus was significantly associated with AD and MD comorbidity in African American participants in the Yale-Penn 1 sample (β = 0.89; 95% CI, 0.57-1.20; P = 2.76 × 10−8). In the independent Yale-Penn 2 sample, the association was also significant (β = 0.83; 95% CI, 0.39-1.28; P = 2.06 × 10−4). Meta-analysis of the 2 samples yielded a more robust association (β = 0.87; 95% CI, 0.61-1.12; P = 2.41 × 10−11). There was no significant association identified in European American participants. Analyses of polygenic risk scores showed that individuals with a higher risk of neuroticism (β = 1.01; 95% CI, 0.50-1.52) or depressive symptoms (β = 0.87; 95% CI, 0.32-1.42) and a lower level of subjective well-being (β = –0.94; 95% CI, –1.46 to –0.42) and educational attainment (β = –1.00, 95% CI, −1.57 to –0.44) had a higher level of AD and MD comorbidity, while larger intracranial (β = 1.07; 95% CI, 0.50 to 1.64) and smaller putamen volumes (β = –1.16; 95% CI, –1.86 to –0.46) were associated with higher risks of AD and MD comorbidity.Conclusions and RelevanceSEMA3A variation is significantly and replicably associated with comorbid AD and MD in African American participants. Analyses of polygenic risk scores identified pleiotropy with neuropsychiatric traits and brain volumes. Further studies are warranted to understand the biological and genetic mechanisms of this comorbidity, which could facilitate development of medications and other treatments for comorbid AD and MD.

Self-Reported Behavioral Disturbances in Older Adults with Hoarding Disorder

Composited International Diagnostic Interview (CIDI). All determinants of interest were assessed with questionnaires that have proven adequate psychometric properties among Dutch older persons. Differences between depressed participants with or without a comorbid ADwere analysed by independent t-tests or chisquare statistics. Multivariate logistic regression analyses were performed to assess the association between previously identified determinants of comorbid AD. Subsequently, recent life-events, early traumatisation, the big five personality characteristics, and sense of mastery were added in separate models. These models were adjusted for the determinants found to be significantly associated with comorbid AD in any of the previous models. Results: More than one third of the patients suffered from any comorbid AD. The most frequent comorbid AD was social phobia (n1⁄462, 17.7%), followed by panic disorder with and without agoraphobia (n1⁄452, 14.9%), agoraphobia (n1⁄436, 10.3%) and finally generalized anxiety disorder (n1⁄433, 9.4%). Having a comorbid AD was consistently associated with a lower age and being female. Nonetheless, other determinants differed across the individual AD. The severity of depressive symptoms was only associated with the presence of a comorbid panic disorder, as was early traumatization. Finally, personality characteristics were associated with comorbid social phobia but not any of the other anxiety disorders. Conclusions: In line with previous studies we found that a fair percentage of depressed older patients suffer from a comorbid AD. Important determinants differ across the individual AD disorders and some determinants are even masked when lumping all AD together as often done. These findings point to the importance of acknowledging the individual comorbid AD. The findings stress the need to examine determinants of individual comorbid AD and by age groups. Knowledge of determinants of comorbid AD in depression may guide development of more specific interventions.

Associations of anxiety disorders, depressive disorders and body weight with hypertension during pregnancy.

The purpose of this study was to prospectively examine the relationships between maternal DSM-IV-TR anxiety disorders, depressive disorders, and body mass index (BMI) with arterial hypertension and blood pressure during pregnancy. In the Maternal Anxiety in Relation to Infant Development (MARI) study, N = 306 women were enrolled in early pregnancy and repeatedly assessed during peripartum period. DSM-IV-TR anxiety and depressive disorders prior to pregnancy, lifetime anxiety/depression liability, and BMI during early pregnancy were assessed with the Composite International Diagnostic Interview for Women (CIDI-V). Based on their prepregnancy status, all participants were assigned to one of the following initial diagnostic groups: no anxiety nor depressive disorder (no AD), pure depressive disorder (pure D), pure anxiety disorder (pure A), and comorbid anxiety and depressive disorder (comorbid AD). Blood pressure measurements were derived from medical records. Arterial hypertension during pregnancy was defined by at least two blood pressure values ≥140mmHg systolic and/or ≥90mmHg diastolic. N = 283 women with at least four documented blood pressure measurements during pregnancy were included in the analyses. In this sample, N = 47 women (16.6%) were identified with arterial hypertension during pregnancy. Women with comorbid AD (reference group: no AD) had a significantly higher blood pressure after adjustment for age, parity, smoking, occupation, household income, and education (systolic: linear regression coefficient [β] = 3.0, 95% confidence interval [CI] = 0.2-5.7; diastolic, β = 2.3, 95% CI = 0.1-4.4). Anxiety liability was associated with an increased risk of hypertension (odds ratio [OR] = 1.1, 95% CI = 1.0-1.3) and a higher systolic blood pressure (β = 0.4, 95% CI = 0.0-0.7). The adjusted interaction model revealed a significant interaction between the diagnostic group pure A and BMI for hypertension (ORIT = 1.5, 95% CI = 1.1-2.1). Especially, women with a lifetime history of comorbid anxiety and depression and obese pregnant women with a lifetime history of pure anxiety disorder should be informed about their heightened risk of hypertension, monitored with regular blood pressure measurements, and provided with strategies for prevention and early intervention such as changes in diet and physical activity.

Reliability and validity of the PDS and PSS-I among participants with PTSD and alcohol dependence

The prevalence of alcohol use disorder (e.g., alcohol dependence; AD) among individuals with posttraumatic stress disorder (PTSD) is quite high, with estimates of 52% for men and 30% for women (Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995). There are several interviews and self-report measures of PTSD with good published psychometric properties, and they are routinely used with comorbid AD and PTSD. However, none of these instruments was validated with this population. The current study fills this gap by examining the psychometric properties of the PTSD Symptom Scale-Interview (PSS-I) and the self-report PTSD Diagnostic Scale (PDS) in individuals diagnosed with current PTSD and AD. Both scales comprised of 17 items provide diagnostic and symptom severity information according to DSM-IV-TR criteria. Participants were 167 individuals who were diagnosed with AD and chronic PTSD and were enrolled in a randomized controlled treatment study. Results revealed excellent internal consistency of both the PSS-I and the PDS, good test–retest reliability over a 1-month period, and good convergent validity with the SCID. The specificity of the PSS-I diagnosis of PTSD was better than the PDS diagnosis, the latter exhibiting a greater percentage of false positives. In sum, the results showed that the PSS-I and PDS performed well in this population and can be used with confidence to assess PTSD diagnosis and symptom severity.

Mixed anxiety and depressive disorder before and after psychodynamic group psychotherapy: a 1-year follow-up study

Objective. The aim of our study was to observe the outcome of MADD in comparison with depressive (DD) and anxiety (AD) disorders. Method. Patients treated with 12 weeks of group psychodynamic psychotherapy in a psychiatric day care ward were examined using SCAN 2.1 at admission and 1 year after admission. Treatment was indicated on the basis of diagnosis of ICD-10 – F4–F6. A total of 139 patients were included, 110 (79.1%) of whom were examined at the follow-up point. Results. The prevalence of MADD increased from 22.7% at the baseline to 33.6% at the end. The outcome of MADD was statistically different from the outcome of DD (χ2=18.4, P=0.0025), but not different from the outcome of comorbid DD and AD (χ2=1.8, P=0.84), nor generalized anxiety disorder (χ2=8.1, P=0.15), nor other AD (χ2=5.3, P=0.38). Conclusion. MADD is a useful diagnosis of a transitional or residual form of comorbid DD and AD in some specific population groups. A diagnosis of personality disorder can sustain long-term diagnosis of MADD.

A Genomewide Association Study of Nicotine and Alcohol Dependence in Australian and Dutch Populations

Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10,000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5 x 10(-8)) for ND (rs964170 in ARHGAP10 on chromosome 4, p = 4.43 x 10(-8)) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10(-9)), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10(-9)) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10(-8))). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepresentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be required before the detailed causes of comorbidity between AD and ND are understood.

A Genomewide Association Study of Nicotine and Alcohol Dependence in Australian and Dutch Populations

Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10, 000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p &lt; 5 x 10-8) for ND (rs964170 in ARHGAPlOon chromosome 4, p = 4.43 x 10”8) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10-9), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10-9) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10-8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepre-sentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be requirec before the detailed causes of comorbidity between AC and ND are understood.

CNR1 Variation Modulates Risk for Drug and Alcohol Dependence

Human cannabinoid receptor 1 (CB1), which is encoded by the CNR1 gene, may play a role in the development of substance dependence (SD). Following initial reports of association of CNR1 with SD, we studied multiple markers at this locus in a large case-control sample. Ten CNR1 markers and 38 ancestry-informative markers were genotyped in 451 healthy control subjects and 550 SD (AD and/or DD) patients (including European Americans [EAs] and African Americans [AAs]). Common confounding effects on association analysis of population stratification and admixture, age, and sex were controlled for using regression analysis. Disease risk and protective alleles were fine-mapped using a linkage disequilibrium measure (delta). In EAs, risk for each SD subtype significantly increased with the number of "G" alleles at rs6454674 (single nucleotide polymorphisms [SNP]3). SNP3;G(+) (the genotypes containing a G allele) and SNP8;T/T genotypes had significant interaction effects (p = .0003 for comorbid DD and AD, .0002 for DD, and .007 for AD). SNP3 and SNP8 together exerted stronger genetic effects on SD than either did individually. The peak delta values among all the markers were seen for SNP3 and SNP8 (rs806368). We demonstrate that CNR1 variation and interactive effects play important roles in risk for both DD and AD.

Characterizing female bipolar alcoholic patients presenting for initial evaluation

This study examined gender differences of age and race-matched group of bipolar disorder (BPO) patients with comorbid alcohol dependence (AD; n = 65; males = 35, females = 30) to a group of BPO patients without comorbid AD (n = 61; males = 22, females = 39). The two groups were also similar on marital status and frequency of BPO subtypes. The results revealed that female bipolar alcoholic patients were more likely to report depressive symptoms as compared to either male bipolar alcoholics or both male and female non-alcoholic bipolar patients. When compared to male bipolar alcoholics, they had higher frequency of depressed mood, slow motor behavior, low self-esteem, decreased libido, decreased appetite, and higher general anxiety symptoms. On the other hand, female bipolar alcoholics differed from female non-alcoholic bipolar patients on reports of mood lability, depressed mood, low self-esteem, suicidal indicators, decreased libido, and general anxiety symptoms. These results raise the question of whether alcohol increases the frequency of depressive symptoms among female bipolar patients.