Affective disorders and the loudness dependence of the auditory evoked potential: Serotonin and beyond.

Identifying additional noninvasive biomarkers for affective disorders, such as unipolar major depressive disorder (MDD) and bipolar disorder (BD), could aid in the diagnosis and treatment of these prevalent and debilitating neuropsychiatric conditions. One such candidate biomarker is the loudness dependence of the auditory evoked potential (LDAEP), an event-related potential that measures responsiveness of the auditory cortex to different intensities of sound. The LDAEP has been associated with MDD and BD, including therapeutic response to particular classes of antidepressant drugs, while also correlating with several other neuropsychiatric disorders. It has been suggested that increased values of the LDAEP indicate low central serotonergic neurotransmission, further implicating this EEG measure in depression. Here, we briefly review the literature on the LDAEP in affective disorders, including its association with serotonergic signaling, as well as with that of other neurotransmitters such as dopamine. We summarize key findings on the LDAEP and the genetics of these neurotransmitters, as well as prediction of response to particular classes of antidepressants in MDD, including SSRIs versus noradrenergic agents. The possible relationship between this EEG measure and suicidality is addressed. We also briefly analyze acute pharmacologic studies of serotonin and/or dopamine precursor depletion and the LDAEP. In conclusion, the existing literature suggests that serotonin and norepinephrine may modulate the LDAEP in an opposing manner, and that this event-related marker may be of use in predicting response to chronic treatment with particular pharmacologic agents in the context of affective disorders, such as MDD and BD, including in the presence of suicidality.

Gut microbiome in atypical depression.

BACKGROUND: Recent studies showed that immunometabolic dysregulation is related to unipolar major depressive disorder (MDD) and that it more consistently maps to MDD patients endorsing an atypical symptom profile, characterized by energy-related symptoms including increased appetite, weight gain, and hypersomnia. Despite the documented influence of the microbiome on immune regulation and energy homeostasis, studies have not yet investigated microbiome differences among clinical groups in individuals with MDD. METHODS: Fifteen MDD patients with atypical features according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)-5, forty-four MDD patients not fulfilling the DSM-5 criteria for the atypical subtype, and nineteen healthy controls were included in the study. Participants completed detailed clinical assessment and stool samples were collected. Samples were sequenced for the prokaryotic 16S rRNA gene, in the V3-V4 variable regions. Only samples with no antibiotic exposure in the previous 12 months and a minimum of >2000 quality-filtered reads were included in the analyses. RESULTS: There were no statistically significant differences in alpha- and beta-diversity between the MDD groups and healthy controls. However, within the atypical MDD group, there was an increase in the Verrucomicrobiota phylum, with Akkermansia as the predominant bacterial genus. LIMITATIONS: Cross-sectional data, modest sample size, and significantly increased body mass index in the atypical MDD group. CONCLUSIONS: There were no overall differences among the investigated groups. However, differences were found at several taxonomic levels. Studies in larger longitudinal samples with relevant confounders are needed to advance the understanding of the microbial influences on the clinical heterogeneity of depression.

Potential efficacy of dopaminergic antidepressants in treatment resistant anergic-anhedonic depression results of the chronic anergic-anhedonic depression open trial - CADOT.

Introduction: Among treatment-resistant depression (TRD), we identified anergic-anhedonic clinical presentations (TRAD) as putatively responsive to pro-dopaminergic strategies. Based on the literature, non-selective monoamine oxidase inhibitors (MAOI) and dopamine D2 receptor agonists (D2RAG) were sequentially introduced, frequently under the coverage of a mood stabilizer. This two-step therapeutic strategy will be referred to as the Dopaminergic Antidepressant Therapy Algorithm (DATA). We describe the short and long-term outcomes of TRAD managed according to DATA guidelines. Method: Out of 52 outpatients with TRAD treated with DATA in a single expert center, 48 were included in the analysis [severity - QIDS (Quick Inventory of Depressive Symptomatology) = 16 ± 3; episode duration = 4.1 ± 2.7 years; Thase and Rush resistance stage = 2.9 ± 0.6; functioning - GAF (Global Assessment of Functioning) = 41 ± 8]. These were followed-up for a median (1st - 3rd quartile) of 4 (1-9) months before being prescribed the first dopaminergic treatment and remitters were followed up 21 (11-33) months after remission. Results: At the end of DATA step 1, 25 patients were in remission (QIDS <6; 52% [38-66%]). After DATA step 2, 37 patients were in remission (77% [65-89%]) to whom 5 patients with a QIDS score = 6 could be added (88% [78-97%]). Many of these patients felt subjectively remitted (GAF = 74 ± 10). There was a significant benefit to combining MAOI with D2RAG which was maintained for at least 18 months in 30 patients (79% [62-95%]). Conclusion: These results support TRAD sensitivity to pro-dopaminergic interventions. However, some clinical heterogeneities remain in our sample and suggest some improvement in the description of dopamine-sensitive form(s).

Microbiome and immuno-metabolic dysregulation in patients with major depressive disorder with atypical clinical presentation.

Depression is highly prevalent (6% 1-year prevalence) and is the second leading cause of disability worldwide. Available treatment options for depression are far from optimal, with response rates only around 50%. This is most likely related to a heterogeneous clinical presentation of major depression disorder (MDD), suggesting different manifestations of underlying pathophysiological mechanisms. Poorer treatment outcomes to first-line antidepressants were reported in MDD patients endorsing an "atypical" symptom profile that is characterized by preserved reactivity in mood, increased appetite, hypersomnia, a heavy sensation in the limbs, and interpersonal rejection sensitivity. In recent years, evidence has emerged that immunometabolic biological dysregulation is an important underlying pathophysiological mechanism in depression, which maps more consistently to atypical features. In the last few years human microbial residents have emerged as a key influencing variable associated with immunometabolic dysregulations in depression. The microbiome plays a critical role in the training and development of key components of the host's innate and adaptive immune systems, while the immune system orchestrates the maintenance of key features of the host-microbe symbiosis. Moreover, by being a metabolically active ecosystem commensal microbes may have a huge impact on signaling pathways, involved in underlying mechanisms leading to atypical depressive symptoms. In this review, we discuss the interplay between the microbiome and immunometabolic imbalance in the context of atypical depressive symptoms. Although research in this field is in its infancy, targeting biological determinants in more homogeneous clinical presentations of MDD may offer new avenues for the development of novel therapeutic strategies for treatment-resistant depression. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".

Objectively assessed sleep and physical activity in depression subtypes and its mediating role in their association with cardiovascular risk factors.

The aims of this study were to investigate the associations of major depressive disorder (MDD) and its subtypes (atypical, melancholic, combined, unspecified) with actigraphy-derived measures of sleep, physical activity and circadian rhythms; and test the potentially mediating role of sleep, physical activity and circadian rhythms in the well-established associations of the atypical MDD subtype with Body Mass Index (BMI) and the metabolic syndrome (MeS). The sample consisted of 2317 participants recruited from an urban area, who underwent comprehensive somatic and psychiatric evaluations. MDD and its subtypes were assessed via semi-structured diagnostic interviews. Sleep, physical activity and circadian rhythms were measured using actigraphy. MDD and its subtypes were associated with several actigraphy-derived variables, including later sleep midpoint, low physical activity, low inter-daily stability and larger intra-individual variability of sleep duration and relative amplitude. Sleep midpoint and physical activity fulfilled criteria for partial mediation of the association between atypical MDD and BMI, and physical activity also for partial mediation of the association between atypical MDD and MeS. Our findings confirm associations of MDD and its atypical subtype with sleep and physical activity, which are likely to partially mediate the associations of atypical MDD with BMI and MeS, although most of these associations are not explained by sleep and activity variables. This highlights the need to consider atypical MDD, sleep and sedentary behavior as cardiovascular risk factors.

A network analysis of depressive symptoms and metabolomics.

BACKGROUND: Depression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network perspective yields a more complete insight than single outcome-single predictor models. METHODS: We used data from the Netherlands Study of Depression and Anxiety (N = 2498) and leveraged networks capturing associations between 30 depressive symptoms (Inventory of Depressive Symptomatology) and 46 metabolites. Analyses involved 4 steps: creating a network with Mixed Graphical Models; calculating centrality measures; bootstrapping for stability testing; validating central, stable associations by extra covariate-adjustment; and validation using another data wave collected 6 years later. RESULTS: The network yielded 28 symptom-metabolite associations. There were 15 highly-central variables (8 symptoms, 7 metabolites), and 3 stable links involving the symptoms Low energy (fatigue), and Hypersomnia. Specifically, fatigue showed consistent associations with higher mean diameter for VLDL particles and lower estimated degree of (fatty acid) unsaturation. These remained present after adjustment for lifestyle and health-related factors and using another data wave. CONCLUSIONS: The somatic symptoms Fatigue and Hypersomnia and cholesterol and fatty acid measures showed central, stable, and consistent relationships in our network. The present analyses showed how metabolic alterations are more consistently linked to specific symptom profiles.

Characteristics and symptomatology of major depressive disorder with atypical features from symptom to syndromal level.

OBJECTIVE: To explore clinical characteristics and symptomatology of major depressive disorder (MDD) with atypical features based on DSM criteria or only reversed vegetative symptoms. METHOD: A total of 3187 patients who met DSM-IV TR criteria for MDD were enrolled. Demographics and symptomatology covering multiple symptom domains were assessed and compared between three groups of cases: those who met DSM criteria for atypical specifier (the DAD group), those who had at least one reversed vegetative symptoms (hypersomnia or hyperphagia) (the SAD group) without meeting DSM atypical specifier criteria, and those without any reversed vegetative symptoms (the NAD group). RESULTS: The DAD and SAD group accounted for 4.4% and 14.4% of the participants, respectively. The DAD cases were characterized by a highest proportion of hospitalizations, longest duration of current episode and worst quality of life. The DAD and SAD cases were more likely to adopt unhealthy behaviors (smoking and alcohol drinking). Most depressive symptoms related to higher illness severity and treatment resistance were more frequent in the DAD cases, followed by the SAD cases, and least frequent in the NAD cases. LIMITATIONS: A cross-sectional design and a non-validated questionnaire were used. CONCLUSIONS: The findings support the role of DSM defined atypical depression as a valid MDD subtype and provide evidence for clinical utility of the simplified approach of defining atypical features based on only reversed vegetative symptoms. This has implications for illness screening, public health, suicide prevention and better treatment planning for depressed individuals with atypical features even below syndromal level.

Differences in cognitive functions of atypical and non-atypical depression based on propensity score matching.

BACKGROUND: Clinical and etiological heterogeneity have hindered our understanding of depression, thus driving the studies of major depressive disorder (MDD) subtypes. Atypical depression (AD) is a subtype of MDD with atypical features. Cognitive impairment is one of the factors that contribute to the suffering of patients with MDD. Therefore, this study investigated the characteristics and differences in cognitive functioning of AD and non-atypical depression (non-AD) using the MATRICS Consensus Cognitive Battery (MCCB). METHODS: A total of 101 patients with AD and 252 patients with non-AD were assessed with the MCCB and clinical scales. Propensity score matching (PSM) was used to balance confounders between groups. After PSM, between-group differences were compared for cognitive and clinical variables. In addition, multiple linear regression analyses were performed to explore the effects of cognitive and clinical variables on the quality of life. RESULTS: The AD group scored significantly lower in attention/vigilance and social cognition in all cognitive domains than the non-AD group. Attention/vigilance and social cognition were significant positive predictors of quality of life, whereas atypical symptoms and depressive severity were significant negative predictors. CONCLUSIONS: This study suggests significant differences in cognitive functions between the AD and non-AD subtypes. Atypical symptoms and impaired cognition have a negative impact on patients' quality of life. Attention/vigilance and social cognition are worse in AD than non-AD, which the atypical features of patients with AD may explain. The pathological mechanisms and treatment strategies of AD should be further explored in the future to promote individualized treatment strategies.

La depresión atípica se asocia con el síndrome metabólico: una revisión sistemática / Atypical depression is associated with metabolic syndrome: a systematic review

Introducción: La depresión y el síndrome metabólico (SM)son problemas importantes de salud pública, esta revisiónsistemática evaluó si el subtipo atípico de depresión está asociadocon el SM, en comparación con otros subtipos depresivos.Metodología. Dos revisores independientes realizaronbúsquedas en las bases de datos de Medline, Lilacs, PsycInfo,Scopus y Web of Science, hasta mayo de 2021, sin restricciónde idioma, incluidos estudios transversales, de casos ycontroles y de cohortes, que evaluaban a adultos. La calidadmetodológica de los estudios se evaluó mediante la escalade Newcastle-Ottawa. Se adoptaron las directrices PRISMA yesta revisión tiene registró en PROSPERO (CRD42018109762).Resultados. La búsqueda en las bases de datos identificó96 artículos y 6 se incluyeron en esta revisión. Los puntajesde calidad metodológica variaron de 7 a 10 puntos. Laasociación entre depresión atípica y SM se demostró entodas las publicaciones, así como la falta de asociacióncon melancólico y otros subtipos. La prevalencia de SM fuesignificativamente mayor entre las personas con depresiónatípica. Vale la pena señalar que hasta el momento solo sehan realizado pocos estudios que evalúen esta comorbilidad.Conclusiones. SM se asocia con depresión atípica, perono con melancólico u otros subtipos. La identificación decaracterísticas clínicas depresivas distintas parece crucialpara comprender mejor su comorbilidad con SM y dilucidarsus vías fisiopatológicas, ambas necesarias para orientarmejor las estrategias de prevención y tratamiento. (AU)

Introduction: Depression and metabolic syndrome (MetS)are important public health problems. This systematic reviewevaluated whether the atypical subtype of depression isassociated with MetS, when compared to other depressivesubtypes.Methods. Two independent reviewers searched inMedline, Lilacs, PsycInfo, Scopus and Web of Sciencedatabases, up to May 2021, without language restriction,including cross-sectional, case-control, and cohort studies,assessing adults. The methodological quality of the studieswas assessed using the Newcastle-Ottawa Scale. The PRISMAguidelines were adopted and this review was registered inPROSPERO (CRD42018109762).Results. The databases search identified 96 articles and 6was included in this review. The methodological quality scoresranged from 7 to 10 points. The association between atypicaldepression and MetS was demonstrated in all publications,as well as the lack of association with melancholic and othersubtypes. The prevalence of MetS was significantly higheramong individuals with atypical depression. It is worthnoting that only few studies assessing this comorbidity wereconducted so far.Conclusions. MetS is associated with atypical depression,but not with melancholic or other subtypes. The identificationof distinct depressive clinical features seems crucial to betterunderstand its comorbidity with MetS and elucidate itspathophysiological pathways, both necessary to better guideprevention and treatment strategies. (AU)

Depression with atypical neurovegetative symptoms shares genetic predisposition with immuno-metabolic traits and alcohol consumption.

BACKGROUND: Depression is a highly prevalent and heterogeneous disorder. This study aims to determine whether depression with atypical features shows different heritability and different degree of overlap with polygenic risk for psychiatric and immuno-metabolic traits than other depression subgroups. METHODS: Data included 30 069 European ancestry individuals from the UK Biobank who met criteria for lifetime major depression. Participants reporting both weight gain and hypersomnia were classified as ↑WS depression (N = 1854) and the others as non-↑WS depression (N = 28 215). Cases with non-↑WS depression were further classified as ↓WS depression (i.e. weight loss and insomnia; N = 10 142). Polygenic risk scores (PRS) for 22 traits were generated using genome-wide summary statistics (Bonferroni corrected p = 2.1 × 10-4). Single-nucleotide polymorphism (SNP)-based heritability of depression subgroups was estimated. RESULTS: ↑WS depression had a higher polygenic risk for BMI [OR = 1.20 (1.15-1.26), p = 2.37 × 10-14] and C-reactive protein [OR = 1.11 (1.06-1.17), p = 8.86 × 10-06] v. non-↑WS depression and ↓WS depression. Leptin PRS was close to the significance threshold (p = 2.99 × 10-04), but the effect disappeared when considering GWAS summary statistics of leptin adjusted for BMI. PRS for daily alcohol use was inversely associated with ↑WS depression [OR = 0.88 (0.83-0.93), p = 1.04 × 10-05] v. non-↑WS depression. SNP-based heritability was not significantly different between ↑WS depression and ↓WS depression (14.3% and 12.2%, respectively). CONCLUSIONS: ↑WS depression shows evidence of distinct genetic predisposition to immune-metabolic traits and alcohol consumption. These genetic signals suggest that biological targets including immune-cardio-metabolic pathways may be relevant to therapies in individuals with ↑WS depression.

Associations of major depressive disorder and related clinical characteristics with 25-hydroxyvitamin D levels in middle-aged adults.

Background: Vitamin D deficiency has been suggested to contribute to the onset of depression, but published results are inconsistent. The aims of this study were 1) to compare serum 25-hydroxyvitamin D (25(OH)D) levels in patients with depression and non-depressed controls and 2) to examine whether distinct subtypes and symptom severity of depression may vary in their association with 25(OH)D.Methods: The study involved cross-sectional data of n=1169 participants from the BiDirect Study (n=639 patients with clinically diagnosed major depressive disorder (MDD), n=530 controls). Serum 25(OH)D was measured via LS-MS/MS. We performed analysis of covariance to evaluate adjusted means of 25(OH)D levels and multinomial logistic regression to assess the association of depression and its clinical characteristics, namely distinct subtypes and symptom severity, with 25(OH)D status (adjusted for age, sex, education, season of blood sample collection, and lifestyle factors).Results: In total, 45.0% of the participants had adequate 25(OH)D levels (≥20 ng/ml), whereas 24.9% had a deficiency (<12 ng/ml). Patients with MDD had lower 25(OH)D levels than controls (16.7 vs. 19.6 ng/ml, p<0.001). Patients with atypical depression had the lowest levels (14.6 ng/ml). Symptom severity was inversely related to 25(OH)D. Moreover, patients with MDD had a more than 2-times higher odds of 25(OH)D deficiency than controls. Atypical depression showed the highest odds of deficiency.Conclusions: The results support that patients with depression have lower 25(OH)D concentrations than non-depressed individuals. Distinct subtypes, particularly the atypical subtype, may play a special role in this context. Therefore, depression heterogeneity should be considered in future research.

The specific phenotype of depression in recent onset schizophrenia spectrum disorders: A symptom profile and network comparison to recent onset major depressive disorder without psychotic features.

The specific phenotype of depression in recent-onset schizophrenia spectrum disorders (SSD) and its relation to non-psychotic depression is unknown. Symptom profile and network analysis are complementary statistical techniques that may provide important insights into the presentation and relative importance of individual symptoms that give rise to depression. The aim of the current study was to characterise the profile and network of depressive symptoms in SSD and compare it to individuals with major depressive disorder (MDD) without psychotic features. This study involved analysis of baseline data pertaining to 109 individuals with comorbid SSD and depression and 283 with MDD without psychotic features. Study cohorts were the Psychosis Recent Onset GRoningen Survey (PROGR-S) and Youth Depression Alleviation (YoDA) trials, respectively. Profile and network analyses revealed that SSD and MDD differed in the profile and relative importance of individual depressive symptoms. While reported sadness was the primary hallmark of depression in both SSD and MDD, individuals with depression in SSD were more likely to sleep more, and have lower lassitude and pessimism. While sadness had great importance in MDD and SSD, in SSD but not MDD lassitude, sleep, appetite, concentration difficulties, and inability to feel were important in the network of depressive symptoms. The specific phenotype of depression might be different in SSD compared to MDD. Symptom inequivalence or underlying functional mechanisms in SSD might result in depression in SSD that is similar to MDD with atypical features.

Clinical characteristics, seasonal characteristics and related factors in patients with atypical depression / 中华行为医学与脑科学杂志

Objective:To know the clinical characteristics, seasonal pattern and influencing factors of atypical depression(AD) patients.Methods:A total of 203 depressed outpatients of Peking University Sixth Hospital from January 2021 to August 2021 were included.They were assessed with demographic questionnaire, inventory of depressive symptomatology self-report(IDS-SR30) and seasonal pattern assessment questionnaire(SPAQ). According the score of IDS-SR30, all patients were classified as atypical depression(AD) and non-atypical depression(non-AD). The data were analyzed by t-test, non-parametric test and Logistic regression using SPSS 26.0 software. Results:The prevalence of AD among depressed patients was 36.0% (95% CI=29.3%-42.6%). The IDS-30 score of the AD group was (41.59±10.59), and IDS-30 score of the non-AD group was (36.08±13.17), and the difference between the two groups was statistically significant ( t=3.062, P<0.05). The global seasonal score of the AD group was 6 (3, 9), and 17.8% of the AD group had seasonal pattren.The global seasonal score of the non-AD group was 5 (3, 8), and 14.6% of the non-AD group had seasonal pattern.There was no significant difference in the global seasonal score and the proportion of seasonal pattern between the two groups ( Z=0.389, χ2=0.359, P>0.05). Depression patients who were females ( β=1.08, OR=2.95, 95% CI=1.32-6.59, P<0.05), low self-evaluation ( β=0.82, OR=2.27, 95% CI=1.12-4.59, P<0.05)and psychomotor retardation ( β=0.93, OR=2.54, 95% CI=1.33-4.85, P<0.05) were more likely to be diagnosed as AD, and depression patients having mood variation ( β=-0.94, OR=0.39, 95% CI=0.19-0.81, P<0.05) were more likely to be diagnosed as non-AD. Conclusion:Women, low self-evaluation, psychomotor retardation and unobvious mood variation can predict and help to diagnose atypical depression in depressed patients.

Circulating Inflammation Markers Partly Explain the Link Between the Dietary Inflammatory Index and Depressive Symptoms.

BACKGROUND: Depression is a mood disorder characterized by a high rate of resistance to pharmacological treatments, which has often been linked to chronic inflammation. This can be influenced by different environmental factors, in particular pro-inflammatory diets. However, a mediating role of circulating inflammation has never been observed. AIM: To test the association between a dietary inflammatory index (DII®) and continuous depressive symptoms (adapted version of PHQ9) in an Italian population cohort (N=13,301), along with potential explanatory effect of a composite index (INFLA-score) based on four circulating inflammatory biomarkers: C-reactive protein, granulocyte-to-lymphocyte ratio, platelet and white blood cell counts. RESULTS: Significant positive associations were observed between DII and total depressive symptoms (standardized ß (SE) = 0.038 (0.005), p < 0.001), and with two factors tagging somatic (0.012 (0.003), p < 0.001) and cognitive symptoms (0.012 (0.003), p < 0.001), after adjustment for different potential confounders (socioeconomic status, chronic health conditions and lifestyles). These associations were about twice as strong in women than in men. INFLA-score explained a small but significant proportion of the association with total depressive symptoms (0.90-2.30%, p < 0.05), which was mainly driven by granulocyte-to-lymphocyte ratio (1.18-1.65%). This effect was even stronger for the somatic (2.66-4.66%) but not for the cognitive factor (0%). CONCLUSION: These findings support a strong link between inflammatory diet and depression, especially with somatic symptoms and within women. Moreover, they provide novel evidence for a potential explanatory role of circulating inflammation in this association, suggesting new paths for prevention and treatment of major and atypical depression.

An electrophysiological model of major depression: Relevance to clinical subtyping and pharmacological management.

We present a neurochemical model of unipolar major depressive disorder that makes predictions for optimizing pharmacological treatment of this debilitating neuropsychiatric disorder. We suggest that there are two principal electrophysiological subtypes of depression, with the more common one involving a high excitatory/inhibitory (E/I) electrophysiological ratio, and a less common low E/I subtype. The high E/I subtype is paradoxically a variant of previous conceptions of atypical depression, whereas the low E/I subtype is a variant of melancholic depression. We focus on the ratio of norepinephrine (NE) to serotonin (5HT) as primary determinants of E/I ratio, which have opposing effects on mood regulation. We suggest that high NE/5HT (or E/I) ratio depressions should be treated with pharmacological agents that boost 5HT (such as SSRIs) and/or drugs that reduce noradrenergic transmission (such as clonidine, guanfacine, propranolol, prazosin). In contrast, low NE/5HT (or E/I) depressions should be treated with agents that boost NE (such as most tricyclics) and/or drugs that reduce serotonergic transmission. Our model predicts that the rapidly acting antidepressant ketamine (and possibly scopolamine), which has an acutely excitatory electrophysiological profile that may be followed by sustained increased inhibition, should improve the high NE/5HT subtype and worsen the low subtype.

The concept of "food addiction" helps inform the understanding of overeating and obesity: NO.

Overeating is a complex behavioral phenotype in terms of both physiology and psychology. The mere transference of the diagnostic criteria for substance use disorders to define food addiction is too simplistic, for the following reasons: 1) a range of somatic and mental disorders require exclusion; 2) food addiction requires distinction from the physiological need to ingest sufficient calories to maintain a high body weight; 3) intentional weight loss can induce an eating behavior mimicking food addiction; 4) the concept lacks validation, especially in light of the high prevalence of "food addiction" in patients with anorexia nervosa; and 5) this construct has not led to novel and successful treatments for overeating and obesity. The concept of food addiction has the potential to distract from the need for focus on environmental influencers to combat the obesity pandemic.

Linking atypical depression and insulin resistance-related disorders via low-grade chronic inflammation: Integrating the phenotypic, molecular and neuroanatomical dimensions.

Insulin resistance (IR) and related disorders, such as T2DM, increase the risk of major depressive disorder (MDD) and vice versa. Current evidence indicates that psychological stress and overeating can induce chronic low-grade inflammation that can interfere with glutamate metabolism in MDD as well as insulin signaling, particularly in the atypical subtype. Here we first review the interactive role of inflammatory processes in the development of MDD, IR and related metabolic disorders. Next, we describe the role of the anterior cingulate cortex in the pathophysiology of MDD and IR-related disorders. Furthermore, we outline how specific clinical features of atypical depression, such as hyperphagia, are more associated with inflammation and IR-related disorders. Finally, we examine the regional specificity of the effects of inflammation on the brain that show an overlap with the functional and morphometric brain patterns activated in MDD and IR-related disorders.

Associations between depressive symptom profiles and immunometabolic characteristics in individuals with depression and their siblings.

OBJECTIVES: The present study examined associations between immunometabolic characteristics (IMCs) and depressive symptom profiles (DSPs) in probands with lifetime diagnoses of depression and/or anxiety disorders and their siblings. METHODS: Data were from the Netherlands Study of Depression and Anxiety, comprising 256 probands with lifetime diagnoses of depression and/or anxiety and their 380 siblings. Measured IMCs included blood pressure, waist circumference, and levels of glucose, triglycerides, HDL cholesterol, CRP, TNF-α and IL-6. DSPs included mood, cognitive, somatic and atypical-like profiles. We cross-sectionally examined whether DSPs were associated with IMCs within probands and within siblings, and whether DSPs were associated with IMCs between probands and siblings. RESULTS: Within probands and within siblings, higher BMI and waist circumference were associated with higher somatic and atypical-like profiles. Other IMCs (IL-6, glucose and HDL cholesterol) were significantly related to DSPs either within probands or within siblings. DSPs and IMCs were not associated between probands and siblings. CONCLUSIONS: The results suggest that there is a familial component for each trait, but no common familial factors for the association between DSPs and IMCs. Alternative mechanisms, such as direct causal effects or non-shared environmental risk factors, may better fit these results.

Obesity and Depression: Its Prevalence and Influence as a Prognostic Factor: A Systematic Review.

OBJECTIVE: Depression and obesity are two conditions with great impact over global health. This is mainly due to their high prevalence and the morbidity and mortality associated to both. The main aim of the present systematic review is to study the association between obesity and depression and the prognostic implications derived from it. METHODS: A literature review was performed in the PUBMED database. 18 articles were found (9 cross-sectional studies, 6 longitudinal studies and 3 clinical trials), which were reviewed by critical reading after which a summary of the main conclusions was written. RESULTS: These selected articles confirmed that there is indeed a link between depression and obesity, although there are doubts as to the significance of this relationship. Depression is a risk factor for obesity, especially atypical depression and in African-American adolescent males. Obesity is a risk factor for depression, especially in women and for recurrent depressive disorder. The comorbidity between obesity and depression is a risk factor for a bad prognosis illness. CONCLUSION: The relationship between both disorders has been analysed in scientific literature, obtaining significant associations but also contradictory results. The most current data demonstrates that there is a relationship between both entities, although there is no unanimity when it comes to establishing the meaning of this association.