Co-occurring Major Depressive Disorder Research Articles

Familial coaggregation and shared genetic influence between major depressive disorder and gynecological diseases.

The mechanism underlying the co-occurrence of major depressive disorder (MDD) and gynecological diseases remains unclear. This study aimed to investigate the familial co-aggregation and shared genetic loading between MDD and gynecological diseases, namely dysmenorrhea, endometriosis, uterine leiomyomas (UL), and polycystic ovary syndrome (PCOS). Overall, 2,121,632 females born 1970-1999 with parental information were enrolled from the Taiwan National Health Insurance Research Database (NHIRD); 25,142 same-sex twins and 951,779 persons with full-sibling(s) were selected. Genome-wide genotyping data were available for 67,882 unrelated female participants from the Taiwan Biobank linked to the NHIRD. A generalized linear model with a logistic link function was used to examine the associations of individual history, family history in parents/full-siblings/same-sex twins, and polygenic risk scores (PRS) for MDD with the risk of gynecological diseases; generalized estimating equations were used to consider the non-independence of data. Both parents affected with MDD was associated with four gynecological diseases, and its magnitude of association was higher than either affected parent; maternal MDD showed a higher magnitude of association than paternal MDD. Full-siblings of patients with MDD had a higher risk of four gynecological diseases; same-sex twins of patients with MDD had a greater association with dysmenorrhea and PCOS. PRS for MDD was associated with dysmenorrhea and endometriosis. Familial co-aggregation was observed in the co-occurrence of MDD and four gynecological diseases. There exists a shared polygenic liability between MDD and dysmenorrhea and endometriosis. Individuals with MDD-affected relatives or a higher PRS for MDD should be monitored for gynecological diseases.

Exploring mitochondrial blood-based and genetic markers in older adults with mild cognitive impairment and remitted major depressive disorder

Mild cognitive impairment (MCI) is a prodromal stage in aging to possible progression to Alzheimer’s disease and related dementia (ADRD), where co-occurrence of major depressive disorder (MDD) accelerates the progression. Metabolic and mitochondrial abnormalities in ADRD and other neurodegenerative disorders have been widely suggested, while possible mitochondrial dysfunction has been associated with etiopathology of both MCI and MDD. Hence, investigation of mitochondrial markers in MCI, MDD, and presence of both conditions is warranted. In total, 332 older adult participants were included: 168 with MCI, 108 with MCI plus remitted MDD (rMDD), and 56 with rMDD but without MCI. We measured plasma circulating mitochondrial DNA (ccf-mtDNA), lactate, and extracted nuclear mitochondrial encoded (NMt) single-nucleotide variants (SNVs) (n = 312). Non-parametric statistical tests on ccf-mtDNA and lactate levels were performed on the diagnosis, clinical and cardiometabolic variables. Binary sequence kernel association test (SKAT-O) and burden test were performed on NMt-SNV, adjusted for age, race, gender, type II diabetes, and APOE genotype. Lower level of lactate was observed in MCI (KW χ2 = 14.8, P = 0.0024), more specifically, significant differences of lower plasma lactate between MCI only and rMDD, but not between MCI+rMDD and MCI were found, suggesting potential roles in MCI driving lactate lower levels. While higher levels of ccf-mtDNA were observed in APOE-ε4 carrier (χ2 = 5.04, P = 0.05). This relationship was present only in MCI (P = 0.043) and MCI+rMDD groups (P = 0.023). No significant nuclear-encoded mitochondrial gene associations were observed with MCI or MDD. The results suggest decreased level of plasma lactate in individuals with MCI and MCI+rMDD, with inverse correlation with ccf-mtDNA, in addition to effect of APOE-ε4 in further increasing ccf-mtDNA specifically in participants with cognitive impairment. These findings contribute to a deeper understanding of the mitochondrial markers in MCI and MDD, warranting further research to explore the precise roles of mitochondrial abnormalities in the development and progression of MCI.

Major Depression in Comorbidity with Substance use Disorders: Patients' Features and Clinical-Neurobiological Rationale of Antidepressant Treatments.

The frequent co-occurrence of major depressive disorder (MDD) and substance use disorders (SUDs) entails significant clinical challenges. Compared to patients with MDD alone, patients with MDD and SUD often show increased anhedonia, emotional blunting, and impaired cognitive function. These symptoms lead to an inability to control cravings, more substance use, increased relapse rates, and poor adherence to the treatment. This fosters a detrimental cycle leading to more severe depressive symptoms, functional impairment, and chronicity, culminating in heightened morbidity, mortality, and healthcare resource utilization. Data on antidepressant treatment of MDD-SUD patients are inconclusive and often conflicting because of a number of confounding factors in clinical trials or difficulty in dissecting the specific contributions of pharmacological versus psychological interventions in real-world studies. The patient's unique clinical features and specific SUD and MDD subtypes must be considered when choosing treatments. Ideally, drug treatment for MDD-SUD should act on both conditions and address core symptoms such as anhedonia, craving, and cognitive dysfunction while ensuring minimal emotional blunting, absence of drug interactions, and no addictive potential. This approach aims to address unmet needs and optimize the outcomes in a clinical population often underrepresented in treatment paradigms.

Dropout in a clinical trial for comorbid PTSD and MDD among US service members: Are pretreatment characteristics predictive?

Objective Despite effective treatment options for posttraumatic stress disorder (PTSD), many patients do not complete therapy. This includes U.S. active duty service members, yet factors linked to attendance in this population remain understudied and dropout remains difficult to predict. Additionally, most studies have not examined samples with PTSD and co-occurring major depressive disorder (MDD) despite high rates of comorbidity. Method The current study explored predictors of dropout among service members with comorbid PTSD and MDD (N = 94) randomized to cognitive processing therapy enhanced with behavioral activation (BA + CPT) or CPT as part of a clinical trial. Results Using the Fournier approach, only two predictors were associated with lower dropout risk among over 20 examined: shorter duration between pretreatment assessment and Session 1 (p = .041) and past 3-month PTSD treatment engagement (p = .036). Conclusion Results suggest the possible utility of early momentum in starting therapy and leveraging recent treatment to improve attendance. However, this study also highlights the possible limitations of commonly assessed pretreatment factors in predicting attendance and current challenges in measuring dropout risk. Strategies to improve prediction, such as shifting focus to assess modifiable factors and processes more proximal to dropout during treatment, may be needed. Trial registration: ClinicalTrials.gov identifier: NCT02874131.

The effects of deep transcranial magnetic stimulation on Alzheimer’s disease: a case report examining cognitive functioning, memory, and QEEG

ABSTRACT Numerous treatment options are being studied for Alzheimer’s disease (AD) given the rising prevalence of this condition worldwide. Transcranial Magnetic Stimulation (TMS) is a promising option for regulating specific neurological abnormalities pertaining to this condition. This case presents a patient with AD and co-occurring major depressive disorder that received 36 sessions of Deep TMS to the frontal and temporal lobes. This patient experienced improved general cognitive functioning and memory, remission from depression, and reduced slow-frequency theta activity in frontal and temporal sites. Following 7 months of weekly maintenance, additional improvements occurred. This report suggests that Deep TMS may be effective in mitigating AD symptoms, and maintenance sessions are advisable.

Polypharmacy Among Patients With Major Depressive Disorder and Co-occurring Substance Use Disorders in a Psychiatric Hospital Setting: Prevalence and Risk Factors.

Major depressive disorder (MDD) is common among patients admitted to a psychiatric hospital who frequently present with comorbid conditions such as substance use disorders (up to 50%). Polypharmacy (ie, being prescribed 3 or more medications) may be relatively common in dual-diagnosis patients. This study sought to examine prevalence and risk factors associated with psychotropic polypharmacy in hospitalized patients with MDD and co-occurring SUDs. An electronic chart review was conducted with 1315 individuals admitted to a psychiatric hospital; 505 (38.4%) were identified as having co-occurring MDD + SUD. We examined psychotropic polypharmacy and clinical severity to explore risk for concerning drug interactions. Potentially problematic polypharmacy patterns were identified among those with MDD + SUD and were related to negative clinical outcomes, particularly in terms of increased sedation potential for individuals with an opioid use disorder (OUD). Groups at the highest risk for polypharmacy included patients who were female, older in age, lower in functioning, and presenting with a co-occurring OUD. Having an OUD was associated with particularly risky polypharmacy combinations, while having a cannabis use disorder was associated with the least polypharmacy. Results highlight a high prevalence of polypharmacy among a group that has an elevated risk for negative outcomes. There is a continued need to improve identification of complex patient presentations and adjust medications in a hospital setting to improve treatment outcomes and reduce future mortality.

Intranasal Esketamine administration in catatonia: a case report.

IntroductionCatatonia is a complex psychomotor syndrome that often goes unrecognized and, consequently, untreated. Prompt and correct identification of catatonia allows for highly effective treatment and prevention of possible complications. Benzodiazepines and electroconvulsive therapy (ECT) are the most widely studied treatment methods. However, no uniform treatment method has yet been brought forward and no previous attempts to treat catatonia on a patient suffering concomitant major depressive disorder (MDD) with NMDA receptor antagonists have been documented so far.ObjectivesTo describe the unknown and novel management of catatonia and MDD with intranasal esketamine, a NMDA receptor antagonist.MethodsA 55-year-old woman with a diagnosis of long-standing recurrent major depressive disorder who was admitted to the psychiatric inpatient unit of UniversityHospital Marqués de Valdecilla (Santander, Spain) suffering a complex catatonic, mutative state framed on a severe MDD. Different ineffective therapeutic interventions were deployed during the course of her illness. After failing to improve under conventional pharmacological treatment and ECT, and given the complexity of peripheral venous access on this patient (which disabled the option for iv ketamine use), we decided to initiate compassionate treatment with intranasal esketamine.ResultsIntranasal esketamine was effective in the resolution of patient’s complex catatonic state. Clinical response from catatonia was observed after 6 intranasal esketamine administrations (2-week follow-up), reaching full catatonia and MDD remission after 12 sessions in absence of significant adverse eventsConclusionsEsketamine showed promising effectiveness for the treatment of catatonia in the context of MDD, although further research on this topic is needed.Disclosure of InterestNone Declared

Men's Depression, Externalizing, and DSM-5-TR: Primary Signs and Symptoms or Co-occurring Symptoms?

Men's Depression, Externalizing, and DSM-5-TR: Primary Signs and Symptoms or Co-occurring Symptoms?

Weighted Blankets for Insomnia in Patients with Psychiatric Disorders

According to this study: Weighted blankets have a clinically meaningful effect on insomnia and daytime functioning in patients with co-occurring major depressive disorder, bipolar disorder, generalized anxiety disorder, and attention deficit–hyperactivity disorder.

Neurobiology and Management of Attention-Deficit/Hyperactivity Disorder and Co-Occurring Major Depressive Disorder: Complications and Strategies

Neurobiology and Management of Attention-Deficit/Hyperactivity Disorder and Co-Occurring Major Depressive Disorder: Complications and Strategies

Mental health disorders mediate association of sexual minority identity with cardiovascular disease

BackgroundLittle is known about cardiovascular health disparities for lesbian, gay, or bisexual (LGB) persons and whether these disparities are mediated by mental health disorders due to sexual minority stress. We hypothesize LGB identity is associated with an increased risk of cardiovascular disease (CVD) and that major depressive disorder (MDD) and generalized anxiety disorders (GAD) may mediate this association. MethodsThe National Epidemiologic Survey on Alcohol and Related Conditions is a longitudinal, nationally-representative study of non-institutionalized U.S. adults. We cross-sectionally analyzed the second wave data (2004–2005) comparing 577 self-identified LGB persons to 33,598 heterosexuals. Multiple logistic regression modeling and mediation analysis (the product of coefficients approach) were performed. ResultsLGB persons had significantly higher CVD prevalence [adjusted odds ratio (AOR): 1.5, 95% CI: 1.2–1.9], and were more likely to be diagnosed with MDD (AOR: 1.9, 1.8–2.1), GAD (AOR: 2.2, 1.9–2.4), or co-occurring MDD and GAD (AOR: 2.2, 2.0–2.5). MDD, GAD, and co-occurrence of MDD and GAD significantly mediated 14.3%, 22.2%, and 33.3% of the association of LGB status with increased CVD prevalence, respectively. ConclusionsOur findings identified a 50% increased CVD prevalence among LGB persons and this increased risk was mediated in part by MDD and GAD, both being more prevalent in sexual minority adults.

Major Depressive Disorder and Cardiovascular Disease in African-American Women

ABSTRACTMajor depression is a risk factor for cardiovascular disease (CVD). This study used the National Survey of American Life (NSAL) to examine the co-occurrence of major depressive disorder (MDD) and CVD in a nationally representative sample of African American women (n = 2,216). Results from a series of logistic regression models indicated high rates of MDD and CVD in the sample, and the African American women with MDD were 1.59 times more likely to have CVD compared to those without MDD. High rates of MDD/CVD co-morbidity appeared across those living in and not living in poverty. These individuals demonstrated greater functional impairment and were high users of mental health services. Our findings validate that MDD and CVD co-occur and the need for more holistic interventions are warranted. The interface of co-morbid health conditions is critical to developing integrated models of care. Integrated health care systems are central for improving physical and mental health outcomes. These findings facilitate developing targeted assessment procedures and culturally appropriate treatment interventions. Increased knowledge regarding the role of gender, chronic health conditions, and the burden of mental illness in African American Women provides the opportunity to examine other chronic health conditions co-occurring with MDD.

Comorbidity, age of onset and suicidality in obsessive–compulsive disorder (OCD): An international collaboration

ObjectivesTo collate data from multiple obsessive–compulsive disorder (OCD) treatment centers across seven countries and five continents, and to report findings in relation to OCD comorbidity, age of onset of OCD and comorbid disorders, and suicidality, in a large clinical and ethnically diverse sample, with the aim of investigating cultural variation and the utility of the psychiatric diagnostic classification of obsessive–compulsive and related disorders. MethodsResearchers in the field of OCD were invited to contribute summary statistics on current and lifetime psychiatric comorbidity, age of onset of OCD and comorbid disorders and suicidality in their patients with OCD. ResultsData from 3711 adult patients with primary OCD came from Brazil (n=955), India (n=802), Italy (n=750), South Africa (n=565), Japan (n=322), Australia (n=219), and Spain (n=98). The most common current comorbid disorders were major depressive disorder (28.4%; n=1055), obsessive–compulsive personality disorder (24.5%, n=478), generalized anxiety disorder (19.3%, n=716), specific phobia (19.2%, n=714) and social phobia (18.5%, n=686). Major depression was also the most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n=1874). OCD generally had an age of onset in late adolescence (mean=17.9years, SD=1.9). Social phobia, specific phobia and body dysmorphic disorder also had an early age of onset. Co-occurring major depressive disorder, generalized anxiety disorder and psychotic disorders tended to have a later age of onset than OCD. Suicidal ideation within the last month was reported by 6.4% (n=200) of patients with OCD and 9.0% (n=314) reported a lifetime history of suicide attempt. ConclusionsIn this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these disorders, but this requires further study. Although there do not appear to be significant cultural variations in rates or patterns of comorbidity and suicidality, further research using similar recruitment strategies and controlling for demographic and clinical variables may help to determine whether any sociocultural factors protect against suicidal ideation or psychiatric comorbidity in patients with OCD.

Analysis of treatment patterns and persistence on branded and generic medications in major depressive disorder using retrospective claims data.

BackgroundIn major depressive disorder (MDD), treatment persistence is critical to optimize symptom remission, functional recovery, and health care costs. Desvenlafaxine tends to have fewer drug interactions and better tolerability than other MDD drugs; however, its use has not been assessed in the real world.ObjectiveThe aim of the present study is to compare medication persistence and concomitant MDD drug use with branded desvenlafaxine (Pristiq®) compared with antidepressant drug groups classified as 1) branded selective serotonin reuptake inhibitors (SSRIs; ie, escitalopram [Lexapro™]) and selective serotonin–norepinephrine reuptake inhibitors (SNRIs; ie, venlafaxine [Effexor®], duloxetine [Cymbalta®]) and 2) generic SSRIs/SNRIs (ie, escitalopram, citalopram, venlafaxine, fluvoxamine, fluoxetine, sertraline, paroxetine, and duloxetine).Patients and methodsMDD patients (ICD-9-CM codes 296.2, 296.3), with ≥2 prescription fills for study drugs and 12-month preindex continuous enrollment from the MarketScan Commercial Claims and Encounters Database (2009–2013), were included. Time-to-treatment discontinuation (prescription gap ≥45 days) was assessed using the Kaplan–Meier curve and Cox model. Concomitant MDD drug use was compared.ResultsOf the 273,514 patients included, 14,379 patients were initiated with branded desvenlafaxine, 50,937 patients with other branded SSRIs/SNRIs, and 208,198 patients with generic SSRIs/SNRIs. The number of weeks for treatment discontinuation for branded desvenlafaxine were longer (40.7 [95% CI: 39.3, 42.0]) compared with other branded SSRIs/SNRIs (28.9 [95% CI: 28.4, 29.1]) and generic SSRIs/SNRIs (33.4 [95% CI: 33.1, 33.7]). Adjusting for baseline characteristics, patients who were prescribed with other branded SSRIs/SNRIs were 31% and generic SSRIs/SNRIs were 11% more likely to discontinue treatment compared with branded desvenlafaxine. In sensitivity analysis, the risk of discontinuation was within 10% of branded desvenlafaxine for branded duloxetine, generic escitalopram, and generic venlafaxine. Concomitant MDD drug use was higher among branded desvenlafaxine patients (43.8%) compared with other branded SSRIs/SNRIs (39.8%) and generic SSRIs/SNRIs (36.4%).ConclusionMDD patients on branded desvenlafaxine were more persistent with treatment compared with those on other branded or generic SSRI/SNRI therapies. Future research should include assessments of underlying factors on the treatment persistence in MDD patients.

Quality of Life in Carotid Atherosclerosis: The Role of Co-morbid Mood Disorders.

Introduction/Objective:To study in severe carotid atherosclerosis (CA): the frequency of mood disorders (MD); the impairment of quality of life (QoL); the role of co-morbid MD in such impairment.Methods:Case-control study. Cases: consecutive in-patients with CA (stenosis ≥ 50%). Controls: subjects with no diagnosis of CA randomized from a database of a community survey. Psychiatric diagnosis according to DSM-IV made by clinicians and semi-structured interview, QoL measured by the Short Form Health Survey (SF-12).Results:This is the first study on comorbidity on CA disease and MD in which psychiatric diagnoses are conducted by clinicians according to DSM-IV diagnostic criteria. Major Depressive Disorder (MDD) (17.4% vs 2.72%, P <0.0001) but not Bipolar Disorders (BD) (4.3% vs 0.5%, P = 0.99) was higher in cases (N=46) than in controls (N= 184). SF-12 scores in cases were lower than in controls (30.56±8.12 vs 36.81±6:40; p <0.001) with QoL comparable to serious chronic diseases of the central nervous system. The burden of a concomitant MDD or BD amplifies QoL impairment.Conclusion:Comorbid MD aggravates the impairment of QoL in CA. Unlike autoimmune diseases or degenerative diseases of the Central Nervous System, CA shows a strong risk of MDD than BD.

Aberrant Parasympathetic Stress Responsivity in Pure and Co-Occurring Major Depressive Disorder and Generalized Anxiety Disorder

Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) are highly comorbid; we know little, however, about the shared physiological features of these disorders. In the present study, we examined whether aberrant parasympathetic stress responsivity represents a transdiagnostic process in MDD, GAD, and co-occurring MDD-GAD. Adult women diagnosed with MDD only, GAD only, and co-occurring MDD-GAD and never-disordered controls (CTLs) completed a standardized laboratory task that involved anticipating, confronting, and recovering from a social stressor. Participants’ levels of respiratory sinus arrhythmia (RSA) were measured to index parasympathetic responses. The three clinical groups combined (participants with MDD only, GAD only, and co-occurring MDD-GAD) exhibited a similar pattern of RSA responsivity that differed significantly from that of the CTL group. Specifically, whereas CTL participants exhibited a sharp decrease in RSA when confronting the stressor and a sharp increase in RSA when recovering immediately following the stressor, the clinical participants exhibited a blunted response pattern that involved weaker fluctuations in RSA when confronting and recovering from the stressor. There were no significant differences among the three clinical groups in RSA responses. Interestingly, clinical and CTL participants did not differ in self-reported fluctuations in negative emotional arousal. Finally, for clinical participants patterns of RSA reactivity to the acute stressor were associated differentially with trait rumination and worry as maladaptive forms of emotion regulation. These findings support the formulation that aberrant parasympathetic stress responsivity is a shared feature of MDD, GAD, and co-occurring MDD-GAD that is characterized by diminished reactivity to and recovery from stress.

Concomitant depression and anxiety negatively affect pain outcomes in surgically managed young patients with trigeminal neuralgia: Long-term clinical outcome

Background:Onset of trigeminal neuralgia (TN) is uncommon in young adults with less favorable benefit from surgical interventions. The aim of this study was to evaluate the role of concomitant psychosomatic disorders in long-term surgical outcomes in this population.Methods:Twenty-one patients younger than 30 years of age were diagnosed initially as having medically refractory TN, and each patient underwent microvascular decompression (MVD) as initial surgical management. Correlation of clinical outcome and psychosomatic disorders (DSM-IV) was evaluated during a 15-year interval.Results:A total of 93 procedures were performed for the management of TN and subsequent iatrogenic craniofacial pain disorders. At a median of 81 months, 8 of 21 patients were free of facial pain. Fourteen patients with concomitant major depressive disorder (MDD) or other anxiety disorders underwent a higher median of procedures compared with 7 patients without known MDD or anxiety (4.5 versus 1 intervention, P = 0.038). Two of 14 patients who were diagnosed with MDD or other anxiety disorders were free of craniofacial pain, whereas 6 of 7 patients without mood or anxiety disorders were free of craniofacial pain (P = 0.0005). Thirteen patients developed treatment-related complications that required further surgical procedures. Presence of MDD or other anxiety disorders was associated with higher rate of complications (P = 0.026). One patient with past medical history of severe anxiety died of unknown causes.Conclusions:In young patients with TN, comorbid MDD or anxiety disorders was associated with seeking multiple invasive procedures in multiple academic centers with limited benefit and high rates of surgical induced complications.

Generalized Anxiety Disorder and Major Depressive Disorder in Pregnant and Postpartum Women: Maternal Quality of Life and Treatment Outcomes

Comorbid generalized anxiety disorder (GAD) and major depressive disorder (MDD) in perinatal women is often under-diagnosed, resulting in suboptimal treatment and leading to significant maternal dysfunction. We describe a prospective, longitudinal study of the course, treatment outcomes, and quality of life (QoL) in pregnant and postpartum women with MDD and anxiety disorders. Two separate cohorts of women were recruited through the Reproductive Mental Health Program, Women's and Children's Hospital, Vancouver, British Columbia, for pharmacotherapy of depressed mood. One cohort was recruited during pregnancy and followed to one month postpartum; the other cohort was recruited postpartum and followed for 12 weeks. All women met the DSM-5 criteria for MDD and anxiety disorders. This non-lactating perinatal population completed measures of depression, anxiety, worry symptoms, and QoL at multiple study visits. Depressed women with GAD or excessive worry were compared to those without GAD in each cohort. Analysis revealed that despite the majority of women with MDD having remission of symptoms with treatment, those with postpartum GAD displayed a poorer quality of life, with persistent worry symptoms, and their illness was slower to remit. Pregnant depressed women with uncontrollable worry (a GAD indicator) showed a lower probability of achieving remission of symptoms with treatment than those without uncontrollable worry. All pregnant and postpartum women with GAD and MDD responded to pharmacotherapy, and the majority attained complete remission of MDD. However, their GAD symptoms persisted, and their QoL was compromised. Given the chronic debilitating course of concomitant MDD and GAD in the perinatal population, it is essential to focus on adjunctive therapies to aim for full recovery.

Erythrocyte fatty acid profiles and plasma homocysteine, folate and vitamin B6 and B12 in recurrent depression: Implications for co-morbidity with cardiovascular disease

Oxidative stress induced interactions between fatty acid (FA) and one-carbon metabolism may be involved in co-occurrence of major depressive disorder (MDD) and cardiovascular disease (CVD), which have been scarcely studied together. In 137 recurrent MDD-patients vs. 73 age- and sex-matched healthy controls, we simultaneously measured key components of one-carbon metabolism in plasma (homocysteine, folate, vitamins B6 and B12), and of FA-metabolism in red blood cell membranes [main polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) and structural FA-indices (chain length, unsaturation, peroxidation)]. Results show significant positive associations of folate with EPA, DHA, and the peroxidation index, which were similar in patients and controls. After correction for confounders, these associations were lost except for EPA. Associations between B-vitamins and FA-parameters were non-significant, but also similar in patients and controls. Homocysteine and DHA were significantly less negatively associated in patients than in controls. In conclusion, these data indicate similarities but also differences in associations between parameters of one-carbon and FA-metabolism in recurrent MDD patients vs. controls, which may reflect differences in handling of oxidative stress. Further research should test the consequences of these differences, particularly the premature development of CVD in MDD.

Antidepressant effectiveness of deep Transcranial Magnetic Stimulation (dTMS) in patients with Major Depressive Disorder (MDD) with or without Alcohol Use Disorders (AUDs): A 6-month, open label, follow-up study

IntroductionCo-occurrence of Major Depressive (MDD) and Alcohol Use Disorders (AUDs) is frequent, causing more burden than each disorder separately. Since the dorsolateral prefrontal cortex (DLPFC) is critically involved in both mood and reward and dysfunctional in both conditions, we aimed to evaluate the effects of dTMS stimulation of bilateral DLPFC with left prevalence in patients with MDD with or without concomitant AUD. MethodsTwelve MDD patients and 11 with concomitant MDD and AUD (MDD+AUD) received 20 dTMS sessions. Clinical status was assessed through the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions severity scale (CGIs), craving through the Obsessive Compulsive Drinking Scale (OCDS) in MDD+AUD, and functioning with the Global Assessment of Functioning (GAF). ResultsThere were no significant differences between the two groups in sociodemographic (age, sex, years of education and duration of illness) and baseline clinical characteristics, including scores on assessment scales. Per cent drops on HDRS and CGIs scores at the end of the sessions were respectively 62.6% and 78.2% for MDD+AUD, and 55.2% and 67.1% for MDD (p<0.001). HDRS, CGIs and GAF scores remained significantly improved after the 6-month follow-up. HDRS scores dropped significantly earlier in MDD+AUD than in MDD LimitationsThe small sample size and factors inherent to site and background treatment may have affected results. ConclusionsHigh frequency bilateral DLPFC dTMS with left preference was well tolerated and effective in patients with MDD, with or without AUD. The antidepressant effect of dTMS is not affected by alcohol abuse in patients with depressive episodes. The potential use of dTMS for mood modulation as an adjunct to treatment in patients with a depressive episode, with or without alcohol abuse, deserves further investigation.