Psychotic Major Depressive Disorder Research Articles

Melancholic features and treatment outcome to selective serotonin reuptake inhibitors in major depressive disorder: A re-analysis of the STAR*D trial

BackgroundMelancholia has been positioned as a qualitatively different form of Major Depressive Disorder (MDD). Some studies have suggested that melancholic MDD patients may show lower remission when receiving treatment with Selective Serotonin Reuptake Inhibitors, but this has not yet been explored in large, representative samples of MDD. MethodsWe used data from the STAR*D, a multisite randomized controlled trial (n = 4041). We defined melancholia status through the BA Melancholia Empirical Index, constructed using items from the Inventory of Depressive Symptomatology (IDSC). The main outcome of interest was symptomatic remission defined as a Quick Inventory of Depressive Symptoms (Clinician version) (QIDS-C) below or equal to 5. Inverse probability weighting was used to control for confounding. Results3827 patients were eligible for this study. Melancholic patients were more likely to be unemployed, never married, to self-report an African American race, and to have a higher depressive severity. The adjusted 4-month probability of remission was 26.9 % (22.0, 45.5) for melancholic and 53.8 % (53.2, 58.5), for nonmelancholic patients. Compared with nonmelancholic, the difference in 4-month probability of remission was −26.9 % (−37.0, −15.6). Results were consistent across sensitivity analyses. LimitationsItems from IDSC were used as a surrogate measure of the BA Melancholia Index, and extrapolation of the results to agents other than citalopram and to psychotic MDD patients requires caution. ConclusionsMelancholic MDD patients showed lower probabilities of remission at 4-months receiving treatment with citalopram. The results of this study show how validly subtyping episodes could contribute to the personalized treatment of depression.

Prevalence and risk factors of suicide attempts in young, first-episode and drug-naïve Chinese Han outpatients with psychotic major depressive disorder.

This study investigates the relationship between psychotic symptoms and suicide attempts in young first-episode, drug-naive Chinese Han outpatients diagnosed with Major Depressive Disorder (MDD). The prevalence of Psychotic Major Depressive Disorder (PMD) was found to be 8.3% among the enrolled MDD patients. The study assessed 1289 participants using various scales to evaluate the severity of clinical symptoms, including the CGI-S, the HAMD, the HAMA, and the PANSS positive subscale. Additionally, thyroid hormone and glucolipid metabolism indicators were examined. The findings indicate that among patients with PMD, 41.12% had recent suicide attempts, while 6.54% had previous suicide attempts. Patients who recently attempted suicide exhibited higher scores on the HAMA and CGI scales, along with elevated serum levels of Thyroid-Stimulating Hormone (TSH) and total cholesterol (TC), as well as higher systolic and diastolic blood pressure. Notably, TSH levels independently correlated with recent suicide attempts in PMD patients, with an impressive area under the receiver operating characteristic curve (AUROC) of 0.923. Furthermore, the subgroup of patients with previous suicide attempts displayed longer illness duration and higher HAMD scores. Duration of illness and HAMD were found to be independently associated with previous suicide attempts among PMD patients, with a combined predictive effect showing a robust AUROC of 0.910. In conclusion, this study highlights the significant prevalence of recent and previous suicide attempts among young Chinese Han outpatients with PMD. The identification of risk factors, especially the link between TSH levels and recent suicide attempts, offers valuable insights for clinicians to develop targeted interventions and preventive strategies for this vulnerable patient population.

Association of serum lipid levels with psychotic symptoms in young, first-episode and drug naïve outpatients with major depressive disorder: A large-scale cross-sectional study

BackgroundMajor depressive disorder (MDD) patients with psychotic symptoms have more complex clinical symptoms and higher relapse rates. The purpose of this study was to compare serum lipid differences between psychotic major depressive disorder (PMD) and non-psychotic major depressive disorder (NPMD) in a large sample of young first-episode drug naïve (FEDN) patients. MethodsWe recruited 1289 young MDD patients. Socio-demographic information, clinical data, and lipid parameters were collected. The Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the positive symptom subscale of the Positive and Negative Syndrome Scale were used to assess patients' depressive, anxiety and psychotic symptoms, respectively. ResultsCompared with the NPMD group, the PMD group had higher HAMD, HAMA scores, and higher TC, TG, and LDL-C levels. Correlation analysis showed that psychotic symptoms were significantly associated with the total score of HAMD and HAMA, and the levels of serum lipid. In addition, logistic regression analysis found that TC was associated with psychotic symptoms in young FEDN MDD patients. ConclusionOur results suggest TC levels may be associated with psychotic symptoms in young MDD patients. The importance of regular psychotic symptom assessment in young MDD patients with high TC levels should be taken into account.

Pharmacological treatment of major depressive disorder according to severity in psychiatric inpatients: results from the AMSP pharmacovigilance program from 2001–2017

The International Classification of Diseases (10th Version) categorizes major depressive disorder (MDD) according to severity. Guidelines provide recommendations for the treatment of MDD according to severity. Aim of this study was to assess real-life utilization of psychotropic drugs based on severity of MDD in psychiatric inpatients. Drug utilization data from the program “Drug Safety in Psychiatry” (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) were analyzed according to the severity of MDD. From 2001 to 2017, 43,868 psychiatric inpatients with MDD were treated in participating hospitals. Most patients were treated with ≥ 1 antidepressant drug (ADD; 85.8% of patients with moderate MDD, 89.8% of patients with severe MDD, and 87.9% of patients with psychotic MDD). More severely depressed patients were more often treated with selective serotonin–norepinephrine reuptake inhibitors and mirtazapine and less often with selective serotonin reuptake inhibitors (p < 0.001 each). Use of antipsychotic drugs (APDs), especially second-generation APDs, increased significantly with severity (37.0%, 47.9%, 84.1%; p < 0.001 each). APD + ADD was the most used combination (32.8%, 43.6%, 74.4%), followed by two ADDs (26.3%, 29.3%, 24.9%). Use of lithium was minimal (3.3%, 6.1% ,7.1%). The number of psychotropic drugs increased with severity of MDD—patients with psychotic MDD had the highest utilization of psychotropic drugs (93.4%, 96.5%, 98.7%; p < 0.001). ADD monotherapy was observed to a lesser extent, even in patients with non-severe MDD (23.2%, 17.1%, 4.4%). Findings reveal substantial discrepancies between guideline recommendations and real-life drug utilization, indicating that guidelines may insufficiently consider clinical needs within the psychiatric inpatient setting.

Association of serum lipid levels with psychotic symptoms in first-episode and drug naïve outpatients with major depressive disorder: a large-scale cross-sectional study

Background Major depressive disorder (MDD) is a prevalent psychiatric disorder, with increasing evidence that patients with MDD display psychotic symptoms. Studies have shown the association between lipid levels and MDD, but few have explored the relationship between lipids and psychotic symptoms in MDD. The objective of this study was to compare the differences of lipid levels between patients with psychotic major depressive disorder (PMD) and those with non-psychotic major depressive disorder (NPMD) in first-episode and drug-naive (FEDN) MDD patients.Methods A total of 1718 outpatients with FEDN MDD were recruited. In addition to collecting basic information, their blood specimens were also collected to detect serum TC, HDL-C, TG, and LDL-C. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, and psychotic symptoms respectively.Results Compared to those with NPMD, those with PMD had higher scores on HAMD, HAMA, and more elevated serum TC, TG, and LDL-C levels, but lower HDL-C levels (all p < 0.05). Further logistic regression analysis showed that TG, the severity of depressive and anxiety symptoms were significantly associated with psychotic symptoms (p < 0.05).Limitations No causal relationship could be drawn due to the cross-sectional design.Conclusions Psychotic symptoms in patients with MDD may be predicted by lipid levels in the future. Our findings suggest that TG seems to predict the presence of current psychotic features among patients with FEDN MDD.

Psychotic symptoms in first-episode and drug naïve patients with major depressive disorder: Prevalence and related clinical factors.

Many patients with major depressive disorder (MDD) have been found to have psychotic symptoms. However, few studies have reported the prevalence of comorbid psychotic symptoms in first-episode drug naïve (FEDN) MDD patients. This study was to investigate the prevalence of psychotic symptoms and related risk factors in a large sample size of FEDN MDD patients in a Chinese population. A total of 573 patients with diagnosis of MDD at their first episode were recruited with their demographic and clinical data. Positive scale of the Positive and Negative Syndrome Scale was utilized for psychotic symptoms, Hamilton Anxiety Rating Scale (HAMA) for anxiety symptoms, and Hamilton Depression Rating Scale (HAMD) for depressive symptoms. The prevalence of psychotic symptoms in these MDD patients was 9.8%. MDD patients with psychotic symptoms had significantly higher HAMD and HAMA total scores than those without psychotic symptoms (both p < .001). A strong association was found between psychotic MDD and anxiety or suicide, with odds ratio of 33.097 for severe anxiety, and 5.012 for suicide. Our results suggest that psychotic symptoms are common in MDD patients at their first episode. The strong association between psychotic MDD and anxiety or suicide attempts demonstrates the importance of reducing anxiety symptoms in the treatment of psychotic MDD patients as well as the necessity to regularly assess suicide risk in MDD patients with psychotic symptoms to better prevent suicidal behavior.

THE ASSOCIATIONS AMONG HISTORY OF PSYCHOSIS, NEUROPSYCHOLOGICAL PERFORMANCE, AND FUNCTIONING IN REMITTED LATER-LIFE MAJOR DEPRESSION

Introduction Observational studies report that people with psychotic major depressive disorder (PMD) have poorer functional outcome than those with non-psychotic major depression (NPMD), but this finding could be explained by less robust recovery and residual symptoms in PMD. In addition, neuropsychological performance is worse in those with PMD than NPMD, both acutely and in remission. The aim of this study was to examine the relative contributions of a history of psychosis and neuropsychological performance to impaired everyday function in patients with remitted later-life major depressive disorder (MDD). We hypothesized that, in later-life patients with MDD, a history of psychotic features and poorer neuropsychological function would be independently associated with poorer everyday functioning, but that poorer neuropsychological performance would be more strongly associated with poorer functioning compared to history of psychosis. In order to place the results in a broader context, we examined everyday functioning in an age- and gender-matched non-psychiatric comparison group. Methods This cross-sectional design study included 73 patients aged 50 years and older with a history of MDD (n = 51 with NPMD and n = 22 with PMD) in sustained remission and 42 non-psychiatric comparison subjects. Sociodemographic, clinical, neuropsychological, and functional data were collected by an investigator blind to the history of psychotic features. Everyday functioning, the dependent variable, was divided into general functioning (measured by participant-report) and IADL performance (measured by observer-rated assessment). The independent variables were i) history of psychosis and ii) neuropsychological performance in the domains of processing speed, memory, and executive function. Relationships between each independent variable and functioning were analyzed using multiple linear regression models. The relative contribution of history of psychosis and neuropsychological performance to functioning was analyzed using multiple regression models with history of psychosis entered in the first step and the neuropsychological variable in the second step. All models included covariates that were potential confounders. We also calculated effect sizes for the difference in functioning between MDD and non-psychiatric comparison participants. Results Patients with PMD exhibited substantial deficits in measures of processing speed and, to a lesser extent, executive function, compared to NPMD patients and to population norms. History of psychosis was independently related to poorer IADL performance (β = 0.262, t = 3.03, p = 0.004) and general functioning (β = -0.29, t = -2.46, p = 0.017). Poorer performance on measures of processing speed (β = -0.468, t = -4.99, p In comparison to non-psychiatric subjects, the effect size of functional impairment in patients with remitted PMD was large (Cohen's d for IADL function = 0.80; Cohen's d for general functioning = 0.97), whereas the impairment was small to moderate in remitted NPMD (Cohen's d for IADL function = 0.10; Cohen's d for general functioning = 0.64). Conclusions Later-life remitted PMD is associated with poorer everyday functioning compared to NPMD, with clinically-significant deficits. However, this relationship is no longer significant when neuropsychological function, especially processing speed, is accounted for. This study advances previous literature by including only patients with rigorously-defined sustained remission and measuring functioning comprehensively using both participant-report and performance-based measures. We will discuss future directions of these research findings, including examining neurobiological correlates of processing speed deficits in remitted PMD. This research was funded by This study was funded by the University Health Network Centre for Mental Health's research grant ($14,000)

RELATIONSHIP OF HAIR CORTISOL CONCENTRATION WITH HISTORY OF PSYCHOSIS, NEUROPSYCHOLOGICAL PERFORMANCE, AND EVERYDAY FUNCTIONING IN REMITTED LATER-LIFE MAJOR DEPRESSIVE DISORDER

Introduction Psychotic features are more prevalent in older adults with depression than in younger depressed adults. Psychotic major depressive disorder (PMD) is associated with poorer neuropsychological performance and poorer everyday functioning, in both acute and remitted states, compared with non-psychotic major depressive disorder (NPMD). In addition, PMD is also associated with more pronounced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including elevated cortisol levels, but it is not known whether this difference between PMD and NPMD persists in remission. The goal of this exploratory study was to test the hypothesis that a history of psychotic features, poorer neuropsychological performance, and poorer everyday functioning were associated with higher cortisol levels in sustained remission of major depressive disorder. If confirmed, it could suggest a possible mechanism for neuropsychological and functional impairment in remitted PMD. In order to examine the relationship between sustained HPA dysfunction in remission and the aforementioned variables, we measured hair cortisol concentration (HCC), a measure of longer-term cortisol exposure. Methods This study used a cross-sectional design and included 60 participants aged 50 years or older with a history of major depressive disorder (n = 17 with NPMD and n = 43 with PMD) in sustained remission and 36 non-psychiatric comparison participants. Hair samples were collected using standardized methods and cortisol concentrations were determined from the first 3-cm hair segment most proximal to the scalp, or from as much hair as was available for participants with shorter hair. This hair segment represents the hair growth over the 3-month period prior to the sampling. HCC was measured in a research laboratory with extensive experience in this analysis using a validated high sensitivity enzyme immunoassay (EIA) that is standard in the field. In order to examine the relationships between HCC and i) history of psychotic features, ii) neuropsychological performance (processing speed, executive function, and verbal memory), and iii) everyday functioning (participant-report general functioning and observer-rated IADL performance), we performed three sets of correlation analyses, one for each variable of interest (point biserial for psychosis history and HCC; Pearson's r for neuropsychological and functional measures). We calculated effect sizes and 95% confidence limits in order to compare HCC results between patient and non-psychiatric comparison groups. HCC data were highly skewed and were log transformed for all analyses. Results NPMD and PMD groups had mean (SD) HCCs of 18.86 (32.97) pg/mg and 12.48 (11.26) pg/mg, respectively. The correlation between HCC and history of psychosis was weak (r = -0.02), as were the correlations between HCC and the neuropsychological measures (r ranging between -0.11 and 0.1). The correlations between HCC and i) IADL performance (r = -0.04) and ii) general functioning (r = -0.074) were also weak. None of these correlations were statistically significant. The mean (SD) HCC for non-psychiatric comparison subjects was 13.86 (20.06) pg/mg. Both effect sizes for the difference between the clinical and non-psychiatric comparison groups were small (0.26 for NPMD versus Comparison group and 0.25 for PMD versus Comparison group). Conclusions This is the first study to assess HCC in PMD and to examine the relationship between HCC and cognition and between HCC and everyday functioning in MDD. We did not find a correlation between HCC and history of psychosis, neuropsychological performance, or functioning in later-life patients with MDD in sustained remission. Further, there was no substantial difference in mean HCC between the patient and non-psychiatric comparison group. There is variability in the literature regarding HCC in MDD and regarding the relationship between HPA-axis function and neuropsychological performance in remitted MDD. Our findings will be discussed in this context. This research was funded by This study was funded by a research grant from the University Health Network Centre for Mental Health ($14,000)

Psychotic Features in Patients With Major Depressive Disorder: A Report From the European Group for the Study of Resistant Depression.

To elucidate the impact of the presence of psychotic features in patients diagnosed with major depressive disorder (MDD) on sociodemographic, psychosocial, clinical, and response characteristics. A total of 1,410 DSM-IV-TR MDD patients were included in the present European multicenter study, which was conducted between 2011 and 2016. Analyses of covariance, χ² tests, and binary logistic regression analyses were performed to explore differences in sociodemographic and clinical variables between MDD patients with and without psychotic symptoms. A prevalence rate of 10.92% for psychotic features was found in MDD. Compared to nonpsychotic MDD patients, those with psychotic features were characterized by a higher likelihood for melancholic characteristics (73.38% vs 59.16%, P = .0006), a higher rate of current suicide risk (60.39% vs 44.27%, P = .0002), greater likelihood of receiving inpatient treatment (55.84% vs 32.01%, P < .0001), greater depressive symptom severity (measured by various rating scales), and more often receiving augmentation/combination treatment strategies in general (81.17% vs 58.12%, P < .0001) and add-on therapy with antipsychotics (50.00% vs 22.69%, P < .0001) and benzodiazepines (47.40% vs 31.29%, P = .0001) in particular. Moreover, psychotic symptoms in MDD were highly predictive of treatment resistance, expressed by a more than 2.2-fold higher likelihood for resistance compared to nonpsychotic MDD patients (79.87% vs 35.75%, P < .0001). Only 3.25% of the patients with psychotic MDD achieved treatment response (vs 27.15% of those with nonpsychotic MDD, P < .0001). These findings suggest that adequate diagnosis of psychotic features in MDD should be ensured in routine clinical care. As a combination of antipsychotics and antidepressants represents the first-line treatment option in psychotic MDD, the finding of a 2-fold higher prescription rate for antipsychotic drugs in psychotic versus nonpsychotic MDD patients reflects the current evidence.

The Korean medication algorithm for depressive disorder: Second revision

AimThis study constitutes a revision of the guidelines for the treatment of major depressive disorder (MDD) issued by the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) 2006. In incorporates changes in the experts׳ consensus that occurred between 2006 and 2012 as well as information regarding newly developed and recently published clinical trials. MethodsUsing a 44-item questionnaire, an expert consensus was obtained on pharmacological treatment strategies for (1) non-psychotic MDD, (2) psychotic MDD, (3) dysthymia and depression subtypes, (4) continuous and maintenance treatment, and (5) special populations; consensus was also obtained regarding (6) the choice of an antidepressant (AD) in the context of safety and adverse effects, and (7) non-pharmacological biological therapies. ResultsAD monotherapy was recommended as the first-line strategy for nonpsychotic depression in adults, children and adolescents, elderly adults, and patients with postpartum depression or premenstrual dysphoric disorder. The combination of AD and atypical antipsychotics (AAP) was recommended for psychotic depression. The duration of the initial AD treatment for psychotic depression depends on the number of depressive episodes. Most experts recommended stopping the initial AD and AAP therapy after a certain period in patients with one or two depressive episodes. However, for those with three or more episodes, maintenance of the initial treatment was recommended for as long as possible. Monotherapy with various selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) was recommended for dysthymic disorder and melancholic type MDD. ConclusionThe pharmacological treatment strategy of KMAP-DD 2012 is similar to that of KMAP-DD 2006; however, the preference for the first-line use of AAPs was stronger in 2012 than in 2006.

Neuroanatomical Classification in a Population-Based Sample of Psychotic Major Depression and Bipolar I Disorder with 1 Year of Diagnostic Stability

The presence of psychotic features in the course of a depressive disorder is known to increase the risk for bipolarity, but the early identification of such cases remains challenging in clinical practice. In the present study, we evaluated the diagnostic performance of a neuroanatomical pattern classification method in the discrimination between psychotic major depressive disorder (MDD), bipolar I disorder (BD-I), and healthy controls (HC) using a homogenous sample of patients at an early course of their illness. Twenty-three cases of first-episode psychotic mania (BD-I) and 19 individuals with a first episode of psychotic MDD whose diagnosis remained stable during 1 year of followup underwent 1.5 T MRI at baseline. A previously validated multivariate classifier based on support vector machine (SVM) was employed and measures of diagnostic performance were obtained for the discrimination between each diagnostic group and subsamples of age- and gender-matched controls recruited in the same neighborhood of the patients. Based on T1-weighted images only, the SVM-classifier afforded poor discrimination in all 3 pairwise comparisons: BD-I versus HC; MDD versus HC; and BD-I versus MDD. Thus, at the population level and using structural MRI only, we failed to achieve good discrimination between BD-I, psychotic MDD, and HC in this proof of concept study.

Effects of S-Ketamine as an Anesthetic Adjuvant to Propofol on Treatment Response to Electroconvulsive Therapy in Treatment-Resistant Depression

Ketamine in electroconvulsive therapy (ECT) anesthesia has been reported to be associated with better seizure quality and longer duration compared with methohexital anesthesia. Furthermore, ketamine may enhance the efficacy of ECT while having rapid independent antidepressant properties itself. However, data on the effects of ketamine with ECT are inconsistent, and there are no reports of S-ketamine. The aim of the present pilot study was to explore the effects of S-ketamine as an adjuvant to propofol on the efficacy, seizure duration, and quality of electroencephalography in patients with treatment-resistant depression. Thirty-two patients with a recurrent severe or psychotic major depressive disorder with treatment resistance to antidepressants were included in the study. For induction of anesthesia, the patients were randomized into 2 study groups. The S-ketamine group first received S-ketamine (0.4 mg/kg) as a bolus and then propofol. The treatment-as-usual group first received saline and then propofol. A statistically significant and clinically relevant reduction in the depression symptom scores was found in both study groups during ECT. There was no difference in the magnitude or speed of response between the study groups, nor was there any difference in the numbers of ECT treatments, seizure thresholds, seizure durations, and the electrical doses either. The patients recovered from anesthesia equally, but the degree of posttreatment disorientation and restlessness was more marked in the S-ketamine group. In conclusion, a subanesthetic adjuvant dose of S-ketamine with propofol may not increase the effects of ECT in patients with treatment-resistant depression. However, S-ketamine was associated with increased posttreatment disorientation and restlessness.

Predicting Diagnostic Change Among Patients Diagnosed With First-EpisodeDSM-IV-TRMajor Depressive Disorder With Psychotic Features

Longitudinal studies beginning from onset of major depressive disorder (MDD) with psychotic features in young adults are rare; therefore, in this study, subjects across a wide age range were included. Since psychotic MDD may be unstable diagnostically, we systematically evaluated such patients prospectively from first episode to ascertain predictors of later diagnostic change. In this prospective naturalistic study, we recruited patients with DSM-IV-TR psychotic MDD from 1989 through 2003 at psychiatric inpatient units in Massachusetts and Italy and followed them from first hospitalization to compare demographic, antecedent, and first-episode clinical characteristics for associations with later changes of diagnosis based on interviews using the Structured Clinical Interview for DSM-III-R, Patient Version. Within a mean (SD) of 4.0 (2.7) years, diagnoses among 107 subjects aged 34.6 (16.2) years (range, 10-82 years) who were experiencing a first lifetime DSM-IV-TR psychotic MDD episode changed in 29.9% to DSM-IV-TR bipolar disorder (18.7%) or schizoaffective disorder (11.2%). Factors associated with stable diagnoses of psychotic MDD included ontological anguish (χ(2) = 13.8, P < .0001), nihilistic delusions (χ(2) = 4.47, P = .034), and weight loss (χ(2) = 4.69, P = .030) at initial syndromal presentation. Factors preceding diagnoses of bipolar disorder included antecedent impulsivity (χ(2) = 9.10, P = .003), ICD-10 mixed states at intake (χ(2) = 19.4, P < .0001), and previous hypomanic symptoms (χ(2) = 13.7, P = .002). Factors predicting later schizoaffective diagnoses included mood-incongruent delusions (χ(2) = 9.17, P = .002) and somatosensory hallucinations (χ(2) = 9.53, P = .033) at intake, previous functional decline (χ(2) = 8.13, P = .008), initial Schneiderian first-rank symptoms (χ(2) = 10.6, P = .005), and meeting criteria for ICD-10 schizoaffective disorder at intake (χ(2) = 24.9, P < .0001). Among patients who initially met DSM-IV-TR criteria for first-episode psychotic MDD, early indications of features typically associated with bipolar disorder or with nonaffective psychoses, respectively, strongly predicted later diagnostic change to bipolar disorder or schizoaffective disorders. The findings support the value of psychopathological details in improving diagnostic and prognostic criteria for complex illnesses.

TPH1, MAOA, Serotonin Receptor 2A and 2C Genes in Citalopram Response: Possible Effect in Melancholic and Psychotic Depression

Background: Serotonergic genes have been widely investigated regarding antidepressant response in major depressive disorder (MDD) but results are still not univocal. Methods: 159 MDD patients treated with citalopram were genotyped and evaluated by the 21-item Hamilton Depression Rating Scale at the beginning and every 4 weeks during the 12-week follow-up. Four serotonin-related genetic variants were tested for association with treatment outcome: tryptophane hydroxylase 1 (TPH1) rs1800532, monoamine oxidase A µVNTR, serotonin 2A receptor rs6311 and serotonin 2C receptor rs6318. The effect of these polymorphisms was tested both in the whole sample and in depressive subtypes with usually higher clinical severity: psychotic and melancholic MDD. Results: No effect on response, remission and symptom improvement was found for the four polymorphisms. However, rs1800532 was found to affect the outcome depending on the MDD subtype: the A allele predicted worse response both in MDD with psychotic (F_{(6, 378)} = 2.90; p = 0.009) and melancholic (F_{(6, 381)} = 2.86; p = 0.0097) features. Conclusions: The A allele at TPH1 rs1800532 may be associated with citalopram efficacy only in melancholic and psychotic MDD. These results suggest the usefulness of investigating the effect of genetic variants in conjunction with specific clinical features.

Cognitive impairment in euthymic major depressive disorder: a meta-analysis

There is evidence to suggest that cognitive deficits might persist beyond the acute stages of illness in major depressive disorder (MDD). However, the findings are somewhat inconsistent across the individual studies conducted to date. Our aim was to conduct a systematic review and meta-analysis of existing studies that have examined cognition in euthymic MDD patients. Following a systematic search across several publication databases, meta-analyses were conducted for 27 empirical studies that compared euthymic adult MDD patients (895 participants) and healthy controls (997 participants) across a range of cognitive domains. The influence of demographic variables and confounding factors, including age of onset and recurrent episodes, was examined. Compared with healthy controls, euthymic MDD patients were characterized by significantly poorer cognitive functions. However, the magnitude of observed deficits, with the exception of inhibitory control, were generally modest when late-onset cases were excuded. Late-onset cases demonstrated significantly more pronounced deficits in verbal memory, speed of information processing and some executive functions. Cognitive deficits, especially poor response inhibition, are likely to be persistent features, at least of some forms, of adult-onset MDD. More studies are necessary to examine cognitive dysfunction in remitted psychotic, melancholic and bipolar spectrum MDD. Cognitive deficits overall appear to be more common among patients with late-onset depression, supporting the theories suggesting that possible vascular and neurodegenerative factors play a role in a substantial number of these patients.

Voxelwise evaluation of white matter volumes in first-episode psychosis

The occurrence of white matter (WM) abnormalities in psychotic disorders has been suggested by several studies investigating brain pathology and diffusion tensor measures, but evidence assessing regional WM morphometry is still scarce and conflicting. In the present study, 122 individuals with first-episode psychosis (FEP) (62 fulfilling criteria for schizophrenia/schizophreniform disorder, 26 psychotic bipolar I disorder, and 20 psychotic major depressive disorder) underwent magnetic resonance imaging, as well as 94 epidemiologically recruited controls. Images were processed with the Statistical Parametric Mapping (SPM2) package, and voxel-based morphometry was used to compare groups (t-test) and subgroups (ANOVA). Initially, no regional WM abnormalities were observed when both groups (overall FEP group versus controls) and subgroups (i.e., schizophrenia/schizophreniform, psychotic bipolar I disorder, psychotic depression, and controls) were compared. However, when the voxelwise analyses were repeated excluding subjects with comorbid substance abuse or dependence, the resulting statistical maps revealed a focal volumetric reduction in right frontal WM, corresponding to the right middle frontal gyral WM/third subcomponent of the superior longitudinal fasciculus, in subjects with schizophrenia/schizophreniform disorder (n=40) relative to controls (n=89). Our results suggest that schizophrenia/schizophreniform disorder is associated with right frontal WM volume decrease at an early course of the illness.

A population-based morphometric MRI study in patients with first-episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects

Many morphometric magnetic resonance imaging (MRI) studies that have investigated the presence of gray matter (GM) volume abnormalities associated with the diagnosis of bipolar disorder (BD) have reported conflicting findings. None of these studies has compared patients with recent-onset psychotic BD with asymptomatic controls selected from exactly the same environment using epidemiological methods, or has directly contrasted BD patients against subjects with first-onset psychotic major depressive disorder (MDD). We examined structural brain differences between (i) BD (type I) subjects and MDD subjects with psychotic features in their first contact with the healthcare system in Brazil, and (ii) these two mood disorder groups relative to a sample of geographically matched asymptomatic controls. A total of 26 BD subjects, 20 subjects with MDD, and 94 healthy controls were examined using either of two identical MRI scanners and acquisition protocols. Diagnoses were based on DSM-IV criteria and confirmed one year after brain scanning. Image processing was conducted using voxel-based morphometry. The BD group showed increased volume of the right dorsal anterior cingulate cortex relative to controls, while the MDD subjects exhibited bilateral foci GM deficits in the dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons). Direct comparison between BD and MDD patients showed a focus of GM reduction in the right-sided dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons) and a trend (p < 0.10, corrected) toward left-sided GM deficits in the dorsolateral prefrontal cortex of MDD patients. When analyses were repeated with scanner site as a confounding covariate the finding of increased right anterior cingulate volumes in BD patients relative to controls remained statistically significant (p=0.01, corrected for multiple comparisons). These findings reinforce the view that there are important pathophysiological distinctions between BD and MDD, and indicate that subtle dorsal anterior cingulate abnormalities may be relevant to the pathophysiology of BD.

Pharmacotherapy for Late-Life Depression

The 2001 expert consensus guidelines for treating major depressive disorder (MDD) in geriatric patients recommended antidepressant treatment in combination with psychotherapy. Recent evidence continues to support the use of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors as first-line agents in the elderly, and although the transdermal monoamine oxidase inhibitor selegilene has shown promise in adult patients, it has not been studied in geriatric depression. Augmentation therapy with atypical antipsychotics or other agents may provide benefits for agitated, psychotic, or resistant MDD in the elderly. The few treatment studies that have been conducted in the geriatric population since the publication of the guidelines have had mixed results and high placebo response rates. More large controlled trials are needed.

The relationship between childhood trauma history and the psychotic subtype of major depression

Increasing evidence exists linking childhood trauma and primary psychotic disorders, but there is little research on patients with primary affective disorders with psychotic features. The sample consisted of adult out-patients diagnosed with major depressive disorder (MDD) at clinic intake using a structured clinical interview. Patients with MDD with (n = 32) vs. without psychotic features (n = 591) were compared as to their rates of different types of childhood trauma. Psychotic MDD patients were significantly more likely to report histories of physical (OR = 2.81) or sexual abuse (OR = 2.75) compared with non-psychotic MDD patients. These relationships remained after controlling for baseline differences. Within the subsample with comorbid post-traumatic stress disorder, patients with psychotic MDD were significantly more likely to report childhood physical abuse (OR = 3.20). Results support and extend previous research by demonstrating that the relationship between childhood trauma and psychosis is found across diagnostic groups.

Response to Treatment with Placebo, Medication or Psychotherapy in Severe Non- Psychotic Major Depressive Disorder

Severe major depressive disorder (MDD) is associated with poorer response to treatment than milder forms of depression, but there is a lack of consensus about the optimal treatment approach. We conducted a qualitative review of the literature for clinical trials of severe MDD in adults (1975 - December 2008), to assess the effects of five treatment approaches: placebo, medication, psychotherapy, combined treatment, and medication augmentation. We found significant variability in treatment outcomes across studies of severe MDD, deriving largely from differences in study design and variability in study samples identified as “severely” depressed. Severely ill patients respond more poorly to placebo and psychotherapy than mildly or moderately depressed patients. Medication monotherapy is superior to psychotherapy alone in the treatment of severe MDD. Combination treatment with medication and psychotherapy shows greater utility in severe, rather than mild or moderate, MDD. Lithium is the best established augmenting agent for severe MDD, particularly in combination with a tricyclic antidepressant. This review indicates the best initial clinical approach to treating severe major depressive disorder is through a combination of medication monotherapy and structured psychotherapy. Future trials in severely ill patients should more fully characterize the clinical and biological aspects of the enrolled patients.