Atypical Depression Research Articles

Correlates of chronic depression in the general population: results from the CoLaus|PsyCoLaus study

PurposePrevious population-based studies have partially provided inconsistent results regarding the co-variates of chronic depression, which were likely to be attributable to methodological limitations. The present paper that compared people with chronic major depressive disorder (MDD), non-chronic MDD and no mood disorder in the community focused on specific atypical and melancholic depression symptoms and subtypes of MDD, family history (FH) of mood disorders, measured physical cardio-vascular risk factors (CVRF), personality traits, coping style and adverse life-events.MethodsData stemmed from a population-based cohort including 3618 participants (female 53%, n=1918; mean age 50.9 years, s.d. 8.8 years). Among them 563 had a lifetime history of chronic MDD, 1060 of non-chronic MDD and 1995 of no mood disorder. Diagnostic and FH information were elicited through semi-structured interviews, CVRF were assessed through physical investigations.ResultsThe major findings were that chronic MDD was associated with increase in appetite/weight and suicidal ideation/attempts during the most severe episode, higher exposure to life-events in adulthood, higher levels of neuroticism, lower levels of extraversion and lower levels of informal help-seeking behavior but less frequent FH of MDD compared to non-chronic MDD.ConclusionChronic MDD is associated with a series of potential modifiable risk factors which are accessible via psychotherapeutic approaches that may improve the course of chronic MDD.

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

BackgroundClinical 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). MethodsA 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. ResultsThe 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. ConclusionsThis 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.

70-year history of studying the effectiveness of therapy of patients with depression with antidepressants - irreversible nonselective monoamine oxidase inhibitors

The history of studying the effectiveness of therapy of patients with depression by irreversible non-selective monoamine oxidase inhibitors (MAOIs) is analyzed and systematized. Authors describe the stages of the appearance of the first data on the effectiveness of treatment by the first representatives (the 50s of the XX century), the targeted study of the effectiveness of the use of numerous «new» representatives and the emergence of disagreements in assessing the power of therapy (the end of the 50s-60s of the XX century), continuing to study the effectiveness of treatment by representatives who remained in clinical practice, and establishing its clinical predictors (80s-90s of the XX century), the appearance of the first data on the effectiveness of therapy for «atypical depression» (1959-1960) and further development of this issue (80s-90s of the XX century). The stage of formation and development of the idea of the effectiveness of treatment for resistant depression (late 70s-90s of the XX century) is characterized. Separately, the history of studying the effectiveness of application in the USSR and Russia (late 50s- 90s of the XX century) is outlined. The current state of the issue of assessing the effectiveness of therapy (the end of the 90s of the XX century - 2022) is shown.

Is chronic fatigue syndrome a novel name for atypical depression? Discussion from a monoamine oxidase inhibitors successful case

Is chronic fatigue syndrome a novel name for atypical depression? Discussion from a monoamine oxidase inhibitors successful case

A viewpoint on aldosterone and BMI related brain morphology in relation to treatment outcome in patients with major depression.

An abundance of knowledge has been collected describing the involvement of neuroendocrine parameters in major depression. The hypothalamic-pituitary-adrenocortical (HPA) axis regulating cortisol release has been extensively studied; however, attempts to target the HPA axis pharmacologically to treat major depression have failed. This review focuses on the importance of the adrenocortical stress hormone aldosterone, which is released by adrenocorticotropic hormone and angiotensin, and the mineralocorticoid receptor (MR) in depression. Depressed patients, in particular those with atypical depression, have signs of central hyperactivation of the aldosterone sensitive MR, potentially as a consequence of a reactive aldosterone release induced by low blood pressure and as a result of low sensitivity of peripheral MR. This is reflected in reduced heart rate variability, increased salt appetite and sleep changes in this group of patients. In addition, enlarged brain ventricles, compressed corpus callosum and changes of the choroid plexus are associated with increased aldosterone (in relation to cortisol). Furthermore, subjects with these features often show obesity. These characteristics are related to a worse antidepressant treatment outcome. Alterations in choroid plexus function as a consequence of increased aldosterone levels, autonomic dysregulation, metabolic changes and/or inflammation may be involved. The characterization of this regulatory system is in its early days but may identify new targets for therapeutic interventions.

A 1-week sleep and light intervention improves mood in premenstrual dysphoric disorder in association with shifting melatonin offset time earlier

To test the hypothesis that 1 week of combined sleep and light interventions (SALI), which phase-advance (shift earlier) melatonin circadian rhythms, improves mood significantly more than phase-delay (shift later) SALI. After a 2-month diagnostic evaluation for premenstrual dysphoric disorder (PMDD per DSM-5 criteria) in a university clinical research setting, 44 participants enrolled in baseline studies were randomized in the luteal phase at home to (A) a phase-advance intervention (PAI): 1 night of late-night wake therapy (LWT: sleep 9 pm–1 am) followed by 7 days of the morning (AM) bright white light (BWL), or (B) a phase-delay intervention (PDI): 1 night of early-night wake therapy (EWT: sleep 3–7 am) plus 7 days of the evening (PM) BWL. After a month of no intervention, participants underwent the alternate intervention. Outcome measures were mood, the melatonin metabolite, 6-sulfatoxymelatonin (6-SMT), and actigraphy (to assess protocol compliance). At baseline, atypical depression correlated positively with phase delay in 6-SMT offset time (r = .456, p = .038). PAI advanced 6-SMT offset from baseline more than PDI (p < .05), and improved raw mood scores more than PDI (p < .05). As hypothesized, percent improvement in mood correlated positively with a phase advance from baseline in 6-SMT offset time (p < .001). Treatment with 1 night of advanced/restricted sleep followed by 7 days of AM BWL (PAI) was more efficacious in reducing PMDD depression symptoms than a PDI; mood improvement occurred in association with phase advance in 6-SMT offset time. Combined SALIs offer safe, efficacious, rapid-acting, well-tolerated, non-pharmacological, non-hormonal, affordable, repeatable home interventions for PMDD. Clinical Trials.gov NCT # NCT01799733.

Atypical depression: frequency of symptoms

Introduction. The relevance of the study is determined by the increase of atypical forms of depression, which is especially characteristic of outpatient affective disorders. In this case, the frequency of occurrence of individual atypical depressive symptoms requires clarification.Aim. To determinate the prevalence of atypical symptoms in patients with depressive disorder.Materials and methods. Patients (87 subjects) with depressive disorder, aged 18–70, who gave inform consent. The selection criterion was the result of psychometric research using The Hospital Anxiety and Depression Scale (HADS): the study included patients who scored more than 7 points. Patients with severe organic insufficiency and neurological diseases, alcohol and substance abuse were excluded. The study used clinical psychometric and statistical methods. The main examination tool is stimulus material in the form of a table with a list of atypical depressive symptoms.Results. Based on the psychometric assessment, patients were divided into two groups: patients with subclinical depression included 19 patients, patients with clinically severe depression included 68 patients. Among patients with subclinical depression, increased anxiety (89.5%), mood reactivity (84.2%), hypersonium (78.9%), hyperphagia (73.7%) and somatized symptoms (73.7%) were most often recorded. Among patients with clinically pronounced depression, increased anxiety (91.2%), somatized symptoms (80.9%), hypersonium (79.4%) and inverted daily rhythm (72.1%) were most common.Conclusion. The data obtained confirm the high prevalence of symptoms of atypical depression among patients with depressive spectrum disorders. The frequent occurrence of anxious and somatized symptoms in the structure of depression, as well as hypersomnia, was demonstrated. It seems relevant to further study the prevalence of separate symptoms of atypical depression.

Valosin-containing protein Asp395Gly mutation in a patient with frontotemporal dementia: a case report

BackgroundVariants in the valosin-containing protein (VCP) gene were identified as one of the causes for inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia (FTD). Previously identified pathogenic variants in VCP are associated with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) pathologically, but p.Asp395Gly VCP was recently reported to cause familial FTD with tauopathy characterized by neurofibrillary tau tangles (NFT) and not FTLD-TDP. We describe the clinical and genetic findings of a patient with p.Asp395Gly valosin-containing protein (VCP), who was diagnosed with FTD without a family history and in the absence of muscle or bone disease comorbidity.Case presentationThe patient was a 62-year-old man, who developed atypical depression at the age of 37 years. Subsequently, he presented with self-centered behavior at the age of 45 years. The self-centered behavior intensified from around the age of 50 years, which was accompanied by the development of executive dysfunction; therefore, he visited our hospital at 52 years of age. Magnetic resonance imaging revealed bilateral frontal lobe atrophy. Brain perfusion single-photon emission computed tomography revealed bilateral frontal lobe hypoperfusion. The patient fulfilled the diagnostic criteria for behavioral variant of FTD. Ten years after the diagnosis, computed tomography of the trunk and limbs, muscle biopsy, and bone scintigraphy revealed the absence of concomitant muscle and bone disease. The concentrations of cerebrospinal fluid (CSF) total tau and phosphorylated tau proteins were 389 pg/mL and 53.2 pg/mL (cut-off: 50 pg/mL), respectively. Genetic analyses were performed using the whole-exome and Sanger sequencing methods. We identified p.Asp395Gly VCP in this patient with pure FTD.Conclusionsp.Asp395Gly VCP was identified in a patient with likely sporadic FTD without concomitant muscle and bone disease. The CSF analysis suggested that our patient may have FTD due to NFT accumulation similar to the familial FTD patients with p.Asp395Gly VCP recently reported. Our findings suggest that a genetic search for the pathogenic variants of VCP should be considered not only for familial FTD, but also for patients with sporadic FTD, even in the absence of comorbid muscle or bone disease.

TNF-α, IL-6 and hsCRP in patients with melancholic, atypical and anxious depression: an antibody array analysis related to somatic symptoms

BackgroundThe association between inflammation and major depressive disorder (MDD) remains poorly understood, given the heterogeneity of patients with MDD.AimsWe investigated inflammatory markers, such as interleukin (IL)-6, high-sensitivity C reactive protein...

Natural Products Inhibitors of Monoamine Oxidases—Potential New Drug Leads for Neuroprotection, Neurological Disorders, and Neuroblastoma

Monoamine oxidase inhibitors (MAOIs) are an important class of drugs prescribed for treatment of depression and other neurological disorders. Evidence has suggested that patients with atypical depression preferentially respond to natural product MAOIs. This review presents a comprehensive survey of the natural products, predominantly from plant sources, as potential new MAOI drug leads. The psychoactive properties of several traditionally used plants and herbal formulations were attributed to their MAOI constituents. MAO inhibitory constituents may also be responsible for neuroprotective effects of natural products. Different classes of MAOIs were identified from the natural product sources with non-selective as well as selective inhibition of MAO-A and -B. Selective reversible natural product MAOIs may be safer alternatives to the conventional MAOI drugs. Characterization of MAO inhibitory constituents of natural products traditionally used as psychoactive preparations or for treatment of neurological disorders may help in understanding the mechanism of action, optimization of these preparations for desired bioactive properties, and improvement of the therapeutic potential. Potential therapeutic application of natural product MAOIs for treatment of neuroblastoma is also discussed.

The association between clinical and biological characteristics of depression and structural brain alterations

BackgroundStructural brain alterations are observed in major depressive disorder (MDD). However, MDD is a highly heterogeneous disorder and specific clinical or biological characteristics of depression might relate to specific structural brain alterations. Clinical symptom subtypes of depression, as well as immuno-metabolic dysregulation associated with subtypes of depression, have been associated with brain alterations. Therefore, we examined if specific clinical and biological characteristics of depression show different brain alterations compared to overall depression. MethodIndividuals with and without depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) (328 participants from three timepoints leading to 541 observations) and the Mood Treatment with Antidepressants or Running (MOTAR) study (123 baseline participants) were included. Symptom profiles (atypical energy-related profile, melancholic profile and depression severity) and biological indices (inflammatory, metabolic syndrome, and immuno-metabolic indices) were created. The associations of the clinical and biological profiles with depression-related structural brain measures (anterior cingulate cortex [ACC], orbitofrontal cortex, insula, and nucleus accumbens) were examined dimensionally in both studies and meta-analysed. ResultsDepression severity was negatively associated with rostral ACC thickness (B = -0.55, pFDR = 0.03), and melancholic symptoms were negatively associated with caudal ACC thickness (B = -0.42, pFDR = 0.03). The atypical energy-related symptom profile and immuno-metabolic indices did not show a consistent association with structural brain measures across studies. ConclusionOverall depression- and melancholic symptom severity showed a dose-response relationship with reduced ACC thickness. No associations between immuno-metabolic dysregulation and structural brain alterations were found, suggesting that although both are associated with depression, distinct mechanisms may be involved.

Study of the efficacy and safety of various pharmacotherapy regimens for atypical depression in the framework of bipolar affective disorder, recurrent depressive disorder, psychogenic depression

IntroductionTo improve the effectiveness of treatment for atypical depression, it is necessary to revise the accumulated experience, taking into account new knowledge and drugs.ObjectivesComparative study of the efficacy and safety of therapy for atypical depression (AtD) in the structure of bipolar affective disorder (BAD), recurrent depressive disorder (RDR) and psychogenic depression (PD).MethodsClinical and clinical follow-up methods examined 77 patients with AtD, of which 35 - with bipolar disorder, 18 - with RDR and 24 - with PD. Patients in all three groups received monotherapy with an antidepressant or a mood stabilizer, or a combination of antidepressant and antipsychotic, antidepressant and mood stabilizer, mood stabilizer and antipsychotic, as well as a combination of antidepressant, antipsychotic and mood stabilizer.ResultsAgomelatine was the most frequently used (27.3%) and effective in reducing MADRS in all groups both in monotherapy and in combination with other drugs. Also in the PD group, escitalopram and vortioxetine were highly effective. Of the antipsychotics, when combined with antidepressants, sulpiride was found to be the most effective. When comparing the tolerance of antidepressants in all groups showed the best results (by the CGI scale), agomelatine and venlafaxine, in the BAR group is also vortioxetine.ConclusionsThe best strategy for effective and safe treatment of atypical depression is the use of modern antidepressant, which does not increase the symptoms of the atypical spectrum and, if necessary, can be supplemented with some antipsychotics.DisclosureNo significant relationships.

Role of MAOI drugs as triggers of manic episodes in bipolar disorders: A case report and a narrative review

IntroductionUse of Monoamine Oxidase Inhibitors (MAOIs) has experimented an important reduction in recent years, being replaced by other antidepressant drugs (ADs) associated with a better safety profile. Its use has been restricted to instructed professionals treating resistant and atypical depression. Thus, treatment-emergent affective switch (TEAS) induced by MAOIs is a rare event nowadays.ObjectivesTo describe a manic episode associated to a one-year-long treatment with phenelzine, a MAOI agent.MethodsWe present the case of a 47-year-old man hospitalized in our acute psychiatric unit after presenting compatible clinical symptoms with a manic episode. He showed severe irritability, decreased need for sleep, pressured speech, increased energy and goal-directed activities. The patient had started phenelzine a year ago for the treatment of major depressive episode resistant to previous pharmacological essayed treatments. No previous history of TEAS was reported, although he had already taken other ADs and mood-stabilizer treatments in the past.ResultsSeveral studies reported the effectiveness of MAOIs for the treatment of monopolar depressive episodes resistant to other ADs, especially when atypical symptoms were observed. Data on the use of MAOIs for the treatment of drug-resistant bipolar depressive episodes is scarce. Few studies have described a good response without showing and increased risk of TEAS.ConclusionsAs MAOIs have fallen out of favour with modern psychiatry, there is scarce evidence on the prevalence of TEAS in patients undergoing treatment with these drugs. Further research is needed in order to accurately define these complex relationships.DisclosureNo significant relationships.

Body mass index and depressive rumination are positively associated with each other only in case of GG genotype of catenin alpha 2 gene rs13412541 variant

IntroductionCatenin alpha 2 gene (CTNNA2) is important in the stability of hippocampal synapses and also in brain development. Our recent paper (Eszlari et al, Pharmaceuticals 2021, 14, 850) has demonstrated that rumination on sad mood mediates the association of CTNNA2 only towards psychiatric symptoms, but not towards cardiovascular risk phenotypes.ObjectivesOur present aim was to test the moderating role of rumination and its two subtypes, brooding and reflection, in genetic associations between CTNNA2 and the same cardiovascular risk phenotypes.Methods633 unrelated subjects from the Budakalasz Health Examination Survey with non-missing phenotypic data, and 160 single-nucleotide CTNNA2 variants remaining after quality control, were included. Linear regression models were run in Plink 1.9 for separate outcomes of body mass index (BMI), and Framingham risk scores for cardiovascular disease, coronary heart disease, myocardial infarction, and stroke. With each variant, predictors were the variant, rumination or its subtype, the variant x rumination interaction, sex, age, and the top ten principal components of the genome. 100,000 label-swapping max(T) permutation was applied for the interaction term within each analysis.ResultsWhile no significant interaction term survived the familywise permutation, two trends emerged. Namely, BMI seems to have positive association with rumination and its maladaptive brooding subtype only in case of GG genotype of rs13412541, otherwise no association can be detected.ConclusionsAlthough replication is needed in larger samples, the relationship between rumination and BMI, conditional on CTNNA2 genotype, can be important in atypical depression, thus may contribute to stratification of depressed patients.DisclosureThe study was supported by the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund (ÚNKP-21-4-II-SE-1); and by 2019-2.1.7-ERA-NET-2020-00005.

Clinical specificities of depression with overvalued ideas in slow progressive schizophrenia

IntroductionDespite the high interest in affective aspects of endogenous depression, the question of overvalued ideas remains unclear.ObjectivesTo determine the clinical features of depression with overvalued ideas in the context of slow progressing schizophrenia.MethodsThe study involved 102 people, including 62 women and 40 men diagnosed with slow progressing schizophrenia, with moderate or severe depression, with the predominance of overvalued ideas (F21 in ICD-10). The control group had 110 people with similar distrubution by sex and age all diagnosed with a depressive state formed in the context of slow progressing schizophrenia, without overvalued ideas. Research methods were mainly clinical-psychopathological and clinical-catamnestic.ResultsIn the majority of observations (62.5%) in the comparison group, showed a uncomplicated form of depression, only limited to affective level. In the (37.5%) left, depression was characterized by a structural polymorphism, in addition to affective disorders, there were other psychopathological syndromes observed. In the main group, an inverse relationship was observed: uncomplicated depression in 29.2% of cases, while the overwhelming majority of cases (70.8%) experienced atypical depressions, disharmony of the affective triad, as well as an increase in the concomitance of neurotic and psychopathic symptoms were observed.ConclusionsThe cohort of patients with slow progressive schizophrenia with depression is heterogeneous, while the features of the course of the disease correlate both with the presence or absence of overvaluated formations in the picture of depression, and with the features of the modification of the overvaluated ideas during the disease.DisclosureNo significant relationships.

Blue-Light Therapy for Seasonal and Non-Seasonal Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ObjectivesTo determine the efficacy and safety of blue-light therapy in seasonal and non-seasonal major depressive disorder (MDD), by comparison to active and inactive control conditions.MethodsWe searched Web of Science, EMBASE, Medline, PsycInfo, and Clinicaltrials.gov through January 17, 2022, for randomized controlled trials (RCTs) using search terms for blue/blue-enhanced, light therapy, and depression/seasonal affective disorder. Two independent reviewers extracted data. The primary outcome was the difference in endpoint scores on the Structured Interview Guide for the Hamilton Depression Rating Scale - Seasonal Affective Disorder (SIGH-SAD) or the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) between blue light and comparison conditions. Secondary outcomes were response (≥ 50% improvement from baseline to endpoint on a depression scale) and remission rates (endpoint score in the remission range).ResultsOf 582 articles retrieved, we included nine RCTs (n = 347 participants) assessing blue-light therapy. Seven studies had participants with seasonal MDD and two studies included participants with non-seasonal MDD. Four studies compared blue light to an inactive light condition (efficacy studies), and five studies compared it to an active condition (comparison studies). For the primary outcome, a meta-analysis with random-effects models found no evidence for the efficacy of blue-light conditions compared to inactive conditions (mean difference [MD] = 2.43; 95% confidence interval [CI], −1.28 to 6.14, P = 0.20); however, blue-light also showed no differences compared to active conditions (MD = −0.11; 95% CI, −2.38 to 2.16, P = 0.93). There were no significant differences in response and remission rates between blue-light conditions and inactive or active light conditions. Blue-light therapy was overall well-tolerated.ConclusionsThe efficacy of blue-light therapy in the treatment of seasonal and non-seasonal MDD remains unproven. Future trials should be of longer duration, include larger sample sizes, and attempt to better standardize the parameters of light therapy.

Clinical features of atypical depression in bipolar and recurrent affective disorders, psychogenic depression

Objective: to perform a comparative study of the clinical features of atypical depression (AtD) in affective disorders of various origins: in bipolar affective disorder (BAD), recurrent depressive disorder (RDR) and psychogenic depression (PD).Patients and methods. A sample of 250 depressed patients aged 18 to 65 years were examined, of which 77 participants (50 women and 27 men) with symptoms of AtD were included to the study. Group 1 included 35 patients with BAD, group 2 – 18 patients with RDR, and group 3 – 24 patients with diagnoses including PD. The patients' condition was assessed using the diagnostic criteria for affective disorders according to ICD-10 and DSM-5 with a Montgomery-Asberg Depression Rating Scale (MADRS).Results and discussion. AtD detection rate was 30.8%, including 45.4% in BAD, 23.4% – in RDR, and 31.2% – in PD. AtD manifested at the age of about 20 years, and was more common in women. AtD in BAD occurred more often in individuals with cycloid, hyperthymic, and hysterical features. Affective fluctuations before the disease onset, a significantly greater number of depressive episodes in history were characteristic. The most frequent typical depressive symptoms included: daily and seasonal mood fluctuations, morning deterioration of well-being, decreased appetite. High comorbidity with metabolic endocrine diseases was observed. AtD in RDR often began spontaneously in individuals with emotionally labile, psychasthenic, and hysterical features. The most common typical depressive symptoms included melancholy, derealization, weakness, ideas of self-accusation, suicidal thoughts and attempts. A high comorbidity with cardiovascular diseases was found. AtD in PD occurred more often in psychasthenic individuals. The most characteristic symptoms included: increased appetite, anxiety, asthenia, superficial night sleep, hypochondriacal inclusions. Comorbidity with skin and gastrointestinal diseases was observed.Conclusion. The identified features of the clinical picture and course of AtD in BAD, RDR, and PD can be used for earlier and more accurate evaluation of affective disorders and the adequate treatment administration.

Comparative evaluation of psychopharmacotherapy of atypical depression in bipolar and recurrent affective disorder, psychogenic depression

Objective: to evaluate the treatment effectiveness for atypical depression (AtD) depending on its nosology: in bipolar affective disorder (BAD), recurrent depressive disorder (RDD) and psychogenic depression (PD).Patients and methods. A total of 250 patients with depression were screened, of which 77 patients with symptoms of AtD were enrolled in the study, 35 of them with BAD, 18 with RDD, and 24 with PD. Patients in all three groups received an antidepressant (AD) or a mood stabilizer (MS) monotherapy, or a combination of AD and antipsychotic (A), AD and A, MS and A, as well as a combination of AD, A and MS. The patients' condition was assessed clinically using a specially designed questionnaire and MADRS and CGI scales at the baseline and the 2nd, 3rd, 4th, 6th, 12th weeks of treatment. Quality of life satisfaction was assessed with the Q-LES-Q-SF (Scoring the Quality-of-Life Enjoyment and Satisfaction Questionnaire) scale at the treatment onset and after the 12th week of treatment.Results and discussion. Treatment regimens that included AD were the most eff in all groups of patients with AtD. The proportion of responders among those who received AD for bipolar disorder (75% or more) was significantly higher than among those who did not receive it (˂50%). In the RDD and PD groups, patients responded significantly better to AD monotherapy (RDD – 93.2%; PD – 91.5%) compared to other regimens. Agomelatine was the most frequently used (31.8%) and effective AD in all groups. Also, escitalopram, vortioxetine, and venlafaxine (p˂0.05) showed high efficacy, good tolerance, and absence of side effects that aggravate the main symptoms that characterize AtD. Among the antipsychotics in combination with AD, sulpiride was significantly more effective in patients with PD (p˂0.05). The highest rates of quality of life satisfaction were achieved in the BAD group, the lowest – in patients with PD (p˂0.05), which indirectly indicates the quality of remission, which is determined not only by the degree of reduction of depressive symptoms but also by the patients' subjective perception of their mental state.Conclusion. The inclusion of AD in the AtD treatment regimen significantly increases its effectiveness in patients of all groups, including BAD. AtD treatment should be administered not only taking into account its clinical signs and severity, but also depending on the nosology of the disease, the characteristics of its course. During drug administration, it is necessary to consider the spectrum of side effects, especially those that increase the symptoms of AtD itself.

Predictors of suicidal ideation trajectories in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study

A better understanding of suicidal ideation (SI), including patterns of SI, may help elucidate links between depression, SI, and suicidal behavior. This study sought to identify trajectories of SI in a large, community-based clinical trial of participants with major depressive disorder (MDD) and to investigate the relationships between these trajectories and predictors of interest, including anxiety and anhedonia. A longitudinal latent class analysis was conducted in 3923 participants enrolled in Level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study of citalopram for the treatment of MDD. An unconditional latent class analysis was conducted using SI at study weeks 0, 2, 4, 6, and 9 as the indicators. A multinomial regression was then conducted with SI trajectory as the outcome and anhedonia, severity of depressive symptoms, atypical depression, anxiety, history of suicide attempt, history of substance abuse, history of trauma, and other covariates as the predictors. Four SI trajectories were identified: 1) variable SI; 2) little-to-no SI; 3) persistent SI; and 4) improving SI. Compared to the little-to-no SI trajectory, those with more severe anhedonia were more likely to experience persistent SI, while those with more severe anxiety were more likely to experience improving SI. Factors that distinguish SI trajectories, such as anxiety and anhedonia, may be critical targets for intervention or profiles for prognosis.

Peripheral and central kynurenine pathway abnormalities in major depression

Considerable data relate major depressive disorder (MDD) with aberrant immune system functioning. Pro-inflammatory cytokines facilitate metabolism of tryptophan along the kynurenine pathway (KP) putatively resulting in reduced neuroprotective and increased neurotoxic KP metabolites in MDD, in addition to modulating metabolic and immune function. This central nervous system hypothesis has, however, only been tested in the periphery. Here, we measured KP-metabolite levels in both plasma and cerebrospinal fluid (CSF) of depressed patients (n = 63/36 respectively) and healthy controls (n = 48/33). Further, we assessed the relation between KP abnormalities and brain-structure volumes, as well as body mass index (BMI), an index of metabolic disturbance associated with atypical depression. Plasma levels of picolinic acid (PIC), the kynurenic/quinolinic acid ratio (KYNA/QUIN), and PIC/QUIN were lower in MDD, but QUIN levels were increased. In the CSF, we found lower PIC in MDD. Confirming previous work, MDD patients had lower hippocampal, and amygdalar volumes. Hippocampal and amygdalar volumes were correlated positively with plasma KYNA/QUIN ratio in MDD patients. BMI was increased in the MDD group relative to the control group. Moreover, BMI was inversely correlated with plasma and CSF PIC and PIC/QUIN, and positively correlated with plasma QUIN levels in MDD. Our results partially confirm previous peripheral KP findings and extend them to the CSF in MDD. We present the novel finding that abnormalities in KP metabolites are related to metabolic disturbances in depression, but the relation between KP metabolites and depression-associated brain atrophy might not be as direct as previously hypothesized.