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We here present the development and validation of the Verbal Affective Memory Test-24 (VAMT-24). First, we ensured face validity by selecting 24 words reliably perceived as positive, negative or neutral, respectively, according to healthy Danish adults’ valence ratings of 210 common and non-taboo words. Second, we studied the test's psychometric properties in healthy adults. Finally, we investigated whether individuals diagnosed with Seasonal Affective Disorder (SAD) differed from healthy controls on seasonal changes in affective recall. Recall rates were internally consistent and reliable and converged satisfactorily with established non-affective verbal tests. Immediate recall (IMR) for positive words exceeded IMR for negative words in the healthy sample. Relatedly, individuals with SAD showed a significantly larger decrease in positive recall from summer to winter than healthy controls. Furthermore, larger seasonal decreases in positive recall significantly predicted larger increases in depressive symptoms. Retest reliability was satisfactory,rs ≥ .77. In conclusion, VAMT-24 is more thoroughly developed and validated than existing verbal affective memory tests and showed satisfactory psychometric properties. VAMT-24 seems especially sensitive to measuring positive verbal recall bias, perhaps due to the application of common, non-taboo words. Based on the psychometric and clinical results, we recommend VAMT-24 for international translations and studies of affective memory. [ABSTRACT FROM PUBLISHER]

Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter-linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P < 0.001). Further, the change in serotonin transporter was sex- (P = 0.02) and genotype- (P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media-1vid110.1093/brain/aww043_video_abstractaww043_video_abstract. [ABSTRACT FROM AUTHOR]

Background: The 5-HT4 receptor provides a novel potential target for antidepressant treatment. No studies exist to elucidate the 5-HT4 receptor's in vivo distribution in the depressed state or in populations that may display trait markers for major depression disorder (MDD). The aim of this study was to determine whether familial risk for MDD is associated with cerebral 5-HT4 receptor binding as measured with [11C]SB207145 brain PET imaging. Familial risk is the most potent risk factor of MDD. Methods: We studied 57 healthy individuals (mean age 36 yrs, range 20-86; 21 women), 26 of which had first-degree relatives treated for MDD. Results: We found that having a family history of MDD was associated with lower striatal 5-HT4 receptor binding (p = 0.038; in individuals below 40 years, p = 0.013). Further, we found evidence for a "risk-dose effect" on 5-HT4 receptor binding, since the number of first-degree relatives with a history of MDD binding correlated negatively with 5-HT4 receptor binding in both the striatum (p = 0.001) and limbic regions (p = 0.012). Conclusions: Our data suggest that the 5-HT4 receptor is involved in the neurobiological mechanism underlying familial risk for depression, and that lower striatal 5-HT4 receptor binding is associated with increased risk for developing MDD. The finding is intriguing considering that the 5-HT4 receptor has been suggested to be an effective target for antidepressant treatment. [ABSTRACT FROM AUTHOR]

Saliva samples are easy to collect and are applicable for home-sampling, e.g. when studying HPA-axis dynamics to characterize diurnal cortisol profiles and the cortisol awakening response. However, the storing and transport conditions might be critical in the home-sampling approach. Here, we tested the stability of saliva cortisol in samples stored at different temperatures and after repeated thawing-freezing cycles when measured with an Enzyme Immuno Assay (EIA). Thirteen healthy volunteers, six women and seven men, mean age 31 (range 26-49) years collected saliva either in the morning hours (08:00-10:00 h) or before lunch (11:00-12:00 h). Storage at six different conditions were tested: Storage at − 18°C, − 4°C, 4°C and room temperature for 72 h. One condition tested was at − 18°C for 72 h and then kept in an envelope for 72 h with a freezing element in room temperature surroundings where after it was stored at − 80°C. The last tube was stored directly at − 80°C and served as the 'gold standard'. The saliva samples were assayed using Salivary Cortisol Diagnostic EIA. Differences in cortisol measurements between each of the five conditions and the 'gold standard' (− 80°C) were evaluated by one-sample t-test. No significant differences were observed. This indicates that an EIA method can be used reliably when measuring salivary cortisol samples obtained by home-sampling including a postal delivery. [ABSTRACT FROM AUTHOR]

Abstract: In patients with Alzheimer''s disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT2A) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT2A receptor and the serotonin transporter binding, the latter as a measure of serotonergic projections and neurons. Twelve patients with AD (average Mini Mental State Examination [MMSE]: 24) and 11 healthy age-matched subjects underwent positron emission tomography (PET) scanning with [18F]altanserin and [11C]N,N-Dimethyl-2-(2-amino-4-cyanopheylthio)benzylamine ([11C]DASB). Overall [18F]altanserin binding was markedly reduced in AD by 28%–39% (p = 0.02), whereas the reductions in [11C]DASB binding were less prominent and mostly insignificant, except for a marked reduction of 33% in mesial temporal cortex (p = .0005). No change in [11C]DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT2A receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections. [Copyright &y& Elsevier]

The article discusses a study on the differential effects of Methylenedioxymethamphetamine (MDMA) and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin2A receptor levels using positron emission tomography (PET) in vivo SERT and serotonin2A receptor binding. Participants were screened to assess history of alcohol, tobacco and illegal drug use as well as current and previous psychiatric symptoms. The results showed evidence that MDMA-preferring users (MPUs) have profound reductions in cerebral SERT binding.

Abstract: There is a large body of evidence that the serotonergic system plays an important role in the transmission and regulation of pain. Here we used positron emission tomography (PET) with the serotonin transporter (SERT) tracer [11C]DASB to study the relationship between SERT binding in the brain and responses to noxious heat stimulation in a group of 21 young healthy volunteers. Responses to noxious heat stimuli were assessed in a separate psychophysical experiment and included measurements of pain threshold, pain tolerance, and responses to phasic noxious heat stimuli and to a long lasting (7-minute) tonic noxious heat stimulus. PET data were analyzed using both volume-of-interest (VOI) and voxel-based approaches. VOI analysis revealed a significant negative correlation between tonic pain ratings and SERT binding in the hypothalamus (r =−0.59; p =0.008), a finding confirmed by the parametric analysis. The parametric analysis also revealed a negative correlation between tonic pain ratings and SERT binding in the right anterior insula. Measures of regional SERT binding did not correlate with pain threshold or with responses to short phasic suprathreshold phasic heat stimuli. Finally, the VOI analysis revealed a positive correlation between pain tolerance and SERT binding in the hypothalamus (r =0.53; p =0.02) although this was not seen in the parametric analysis. These data extend our earlier observation that cortical 5-HT receptors co-determine responses to tonic but not to phasic pain. The negative correlation between SERT binding in the hypothalamus and insula with tonic pain ratings suggests a possible serotonergic control of the role of these areas in the modulation or in the affective appreciation of pain. [ABSTRACT FROM AUTHOR]

Serotonergic neurotransmission is involved in the regulation of physiological functions such as mood, sleep, memory, and appetite. Within the serotonin transmitter system, both the postsynaptically located serotonin 2A(5-HT2A ) receptor and the presynaptic serotonin transporter (SERT) are sensitive to chronic changes in cerebral 5-HT levels. Additionally, experimental studies suggest that alterations in either the 5-HT2A receptor or SERT level can affect the protein level of the counterpart. The aim of this study was to explore the covariation between cerebral 5-HT2A receptor and SERT in vivo in the same healthy human subjects. Fifty-six healthy human subjects with ameanage of 36 ± 19 years were investigated. The SERT binding was imaged with [ 11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)- benzonitrile (DASB) and 5-HT2A receptor binding with [ 18F]altanserin using positron emission tomography. Within each individual, a regional intercorrelation for the various brain regions was seen with both markers, most notably for 5-HT2A receptor binding. An inverted U-shaped relationship between the 5-HT2A receptor and the SERT binding was identified. The observed regional intercorrelation for both the 5-HT2A receptor and the SERT cerebral binding suggests that, within the single individual, each marker has a set point adjusted through a common regulator. A quadratic relationship between the two markers is consistent with data from experimental studies of the effect on SERT and 5-HT2A receptor binding of chronic changes in 5-HT levels. That is, the observed association between the 5-HT2A receptor and SERT binding could be driven by the projection output from the raphe nuclei, but other explanations are also at hand. [ABSTRACT FROM AUTHOR]

Abstract: There is a large body of evidence that serotonin [5-hydroxytryptamine (5-HT)] plays an important role in the transmission and regulation of pain. Here we used positron emission tomography (PET) to study the relationship between baseline 5-HT2A binding in the brain and responses to noxious heat stimulation in a group of young healthy volunteers. Twenty-one healthy subjects underwent PET scanning with the 5-HT2A antagonist, [18F]altanserin. In addition, participants underwent a battery of pain tests using noxious heat stimulation to assess pain threshold, pain tolerance and response to short-lasting phasic and long-lasting (7-minute) tonic painful stimulation. Significant positive correlations were found between tonic pain ratings and [18F]altanserin binding in orbitofrontal (r = 0.66; p = 0.005), medial inferior frontal (r = 0.60; p = 0.014), primary sensory–motor (r = 0.61; p = 0.012) and posterior cingulate (r = 0.63; p = 0.009) cortices. In contrast, measures of regional [18F]altanserin binding did not correlate with pain threshold, pain tolerance, or suprathreshold phasic pain responses. These data suggest that cortical 5-HT2A receptor availability co-varies with responses to tonic pain. The correlation between [18F]altanserin binding in prefrontal cortex and tonic pain suggests a possible role of this brain region in the modulation and/or cognitive-evaluative appreciation of pain. [Copyright &y& Elsevier]

The serotonin 5-HT2A receptor is suspected to be involved in a number of psychiatric disorders, including schizophrenia. In particular, atypical antipsychotics have antagonistic effects on the 5-HT2A receptors, supporting a specific role of the 5-HT2A receptor in the pathophysiology of this disease. The aim of this study is to investigate cortical and subcortical 5-HT2A binding in neuroleptic-naive schizophrenic patients. Fifteen neuroleptic-naive patients diagnosed with schizophrenia (age 27.5±4.5 years), 11 men and 4 women, and 15 healthy control subjects matched for age (28.5±5.7 years) and gender underwent a 40 min positron emission tomography (PET) study using the 5-HT2A antagonist, [18F]altanserin, as a radioligand. PET images were co-registered to 3 T magnetic resonance images (MRIs) for each individual subject, and ROIs were applied automatically onto the individual MRIs and PET images. The cerebellum was used as a reference region. The binding potential of specific tracer binding (BPp) was used as the outcome measure. No significant difference was seen in cortical receptor distribution between patients and controls. An increase in 5-HT2A receptor binding in the caudate nucleus was detected in the group of schizophrenic patients (0.7±0.1) when compared to the healthy controls (0.5±0.3) (p=0.02). Our results confirm other in vivo findings of no difference in cortical 5-HT2A receptor binding between first-episode antipsychotic-naive schizophrenic patients and age- and gender-matched healthy control subjects. However, a preliminary finding of increased 5-HT2A binding in the caudate nucleus requires further investigation to explore the relation of subcortical and cortical 5-HT2A receptor binding.Neuropsychopharmacology (2008) 33, 2435–2441; doi:10.1038/sj.npp.1301656; published online 20 February 2008 [ABSTRACT FROM AUTHOR]

Rumination is a maladaptive response to distress characteristic of Major Depressive Disorder (MDD). It is unclear to what degree rumination is associated with depression severity prior to treatment and how it responds to antidepressant treatment. Therefore, we evaluated the association between rumination and depression severity in 92 untreated patients with MDD and explored the changes in rumination after initiation of antidepressant medication. We measured rumination using the Rumination Response Scale (RRS) and depression severity with the Hamilton Depression Rating Scale (HDRS 17 or HDRS 6) before and after initiation of 12 weeks of antidepressant treatment. The association between RRS and pre-treatment HDRS 17 was evaluated using a linear regression model. RRS at week 4, 8, and 12 across treatment response categories (remission vs. non-response) were evaluated using a mixed effect model. RRS was positively associated with depression severity prior to treatment at a trend level (p = 0.06). After initiation of treatment RRS decreased significantly (p < 0.0001) and remitters exhibited lower rumination compared to non-responders at week 4 (p = 0.03), 8 (p = 0.01), and 12 (p = 0.007). The study had no placebo group. Although pre-treatment rumination did not significantly associate with depressive symptoms, rumination was closely connected to change in depressive symptoms. Tormented patients could be reassured that rumination symptoms may be alleviated over the course of antidepressant treatment. • Pre-treatment rumination associate with depression severity at a trend level. • Rumination is connected to change in depressive symptoms during treatment. • Different rumination time-courses are created after 4 weeks of treatment. [ABSTRACT FROM AUTHOR]

• EEG abnormalities are not associated with non-response to escitalopram. • EEG abnormalities are associated with poor verbal memory. • Patients with EEG abnormalities reported greater mood disturbance, particularly anger. EEG brain abnormalities, such as slowing and isolated epileptiform discharges (IEDs), has previously been associated with non-response to antidepressant treatment with escitalopram and venlafaxine, suggesting a potential need for treatment with anticonvulsant property in some patients. The current study aims to replicate the reported association of EEG abnormality and treatment outcomes in an open-label trial of escitalopram for major depressive disorder (MDD) and explore its relationship to mood and cognition. Pretreatment, 6 min eyes-closed resting-state 256-channel EEG was recorded in 91 patients with MDD (age 18–57) who were treated with 10–20 mg escitalopram for 12 weeks; patients could switch to duloxetine after four weeks. A certified clinical neurophysiologist rated the EEGs. IED and EEG slowing was seen in 13.2%, and in 6.6% there were findings with unclear significance (i.e., Wicket spikes and theta activity). We saw no group-difference in remission or response rates after 8 and 12 weeks of treatment or switching to duloxetine. Patients with EEG abnormalities had higher pretreatment mood disturbances driven by greater anger (p =.039) and poorer verbal memory (p =.012). However, EEG abnormality was not associated with improved mood or verbal memory after treatment. Our findings should be interpreted in light of the rarity of EEG abnormalities and the sample size. While we cannot confirm that EEG abnormalities are associated with non-response to treatment, including escitalopram, abnormal EEG activity is associated with poor mood and verbal memory. The clinical utility of EEG abnormality in antidepressant treatment selection needs careful evaluation before deciding if useful for clinical implementation. [ABSTRACT FROM AUTHOR]

Background: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states. Methods: We describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD). Utilizing imaging harmonization and machine learning methods in a large cohort of medication-free, deeply phenotyped MDD participants, patterns of brain alteration are defined in replicable and neurobiologically-based dimensions and offer the potential to predict treatment response at the individual level. International datasets are being shared from multi-ethnic community populations, first episode and recurrent MDD, which are medication-free, in a current depressive episode with prospective longitudinal treatment outcomes and in remission. Neuroimaging data consist of de-identified, individual, structural MRI and resting-state functional MRI with additional positron emission tomography (PET) data at specific sites. State-of-the-art analytic methods include automated image processing for extraction of anatomical and functional imaging variables, statistical harmonization of imaging variables to account for site and scanner variations, and semi-supervised machine learning methods that identify dominant patterns associated with MDD from neural structure and function in healthy participants. Results: We are applying an iterative process by defining the neural dimensions that characterise deeply phenotyped samples and then testing the dimensions in novel samples to assess specificity and reliability. Crucially, we aim to use machine learning methods to identify novel predictors of treatment response based on prospective longitudinal treatment outcome data, and we can externally validate the dimensions in fully independent sites. Conclusion: We describe the consortium, imaging protocols and analytics using preliminary results. Our findings thus far demonstrate how datasets across many sites can be harmonized and constructively pooled to enable execution of this large-scale project. [ABSTRACT FROM AUTHOR]

The dynamic capacity of the hypothalamic-pituitary-adrenal (HPA) axis supports healthy adaptions to stress and play a key role in maintaining mental health. Perinatal adaptations in the HPA-axis dynamics in terms of the Cortisol Awakening Response (CAR), may be involved in dysregulation of perinatal mental health. We aimed to determine if CAR and absolute evening cortisol early postpartum differed from non-perinatal women and evaluate the association between the CAR and maternal mental well-being. The CAR was computed as the area under the curve with respect to increase from baseline from serial home-sampling of saliva across 0–60 minutes from awakening. We evaluated differences in CAR and absolute evening cortisol between postpartum women (N=50, mean postpartum days: 38, SD: ±11) and non-perinatal women (N=91) in a multiple linear regression model. We also evaluated the association between CAR and maternal mental well-being in a multiple linear regression model. We found that healthy postpartum women had a blunted CAR (p<0.001) corresponding to 84% reduction and 80% lower absolute evening cortisol (p<0.001) relative to non-perinatal healthy women. In the postpartum group, there was a trend-level association between lower CAR and higher scores on the WHO Well-Being Index (WHO-5) (p=0.048) and lower Edinburgh Postnatal Depression Scale (EPDS) scores (p=0.04). Our data emphasize the unique hormonal landscape during the postpartum period in terms of blunted CAR and lower absolute evening cortisol in healthy women early postpartum compared to non-perinatal. Our findings show a potential association between a reduced CAR and improved mental well-being during early motherhood, which suggests that reduced CAR might reflect healthy adjustment to early motherhood. • Healthy postpartum women had a blunted CAR corresponding to 84% reduction compared to non-perinatal women • Healthy postpartum women had 80% lower absolute evening cortisol compared to non-perinatal women • We note a potential association between lower CAR and higher well-being postpartum • We suggest that reduced CAR reflects a healthy adjustment to early motherhood. [ABSTRACT FROM AUTHOR]

Background: Postpartum depression (PPD) is the most common postpartum psychiatric disorder, affecting 11–15% of new mothers, and initiatives towards early identification and treatment are essential due to detrimental consequences. Family history of psychiatric disorders is a risk factor for developing psychiatric episodes outside the postpartum period, but evidence of the association between familial risk and PPD is not clear. Hence, the objective of this systematic review is to summarize the current literature on the association between family history of psychiatric disorders and PPD. Methods: This protocol has been developed and reported according to the PRISMA-P guidelines for systematic reviews. A comprehensive literature search will be conducted in PubMed, Embase, and PsycINFO from inception of the databases, supplemented with citation tracking and reference screening of the included studies. Two independent authors will examine all retrieved articles for inclusion in two steps: title/abstract screening and full-text screening. Eligible studies are case-control and cohort studies reporting a risk estimate for the association between family history of psychiatric disorders and PPD. Studies will be assessed for risk of bias using the Newcastle-Ottawa Scale. The association between family psychiatry and PPD will be combined in a meta-analysis using a restricted maximum likelihood method (REML). Heterogeneity will be quantified using I2 and investigated through meta-regression, subgroup and sensitivity analyses, and publication bias will be evaluated via visual inspection of a funnel plot. The overall strength and quality of the findings will be evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. If meta-analysis is not possible, data will be synthesized narratively in text and tables. Discussion: This systematic review will be the first to summarize current knowledge and present an overall estimate for the association between family history of psychiatric disorders and PPD. Evaluation of psychiatric family history as a PPD risk factor is essential to assist early identification of women at high risk of PPD in routine perinatal care. Systematic review registration: PROSPERO ID: 277998 (registered 10th of September 2021). [ABSTRACT FROM AUTHOR]

While several electroencephalogram (EEG)-based biomarkers have been proposed as diagnostic or predictive tools in major depressive disorder (MDD), there is a clear lack of replication studies in this field. Markers that link clinical features such as disturbed wakefulness regulation in MDD with neurophysiological patterns are particularly promising candidates for e.g., EEG-informed choices of antidepressive treatment. We investigate if we in an independent MDD sample can replicate abnormal findings of EEG-vigilance regulation during rest and as a predictor for antidepressive treatment response. EEG-resting state was recorded in 91 patients and 35 healthy controls from the NeuroPharm trial. EEG-vigilance was assessed using the Vigilance Algorithm Leipzig (VIGALL). We compared the vigilance regulation during rest between patients and healthy controls and between remitters/responders and non-remitters/non-responders after eight weeks of SSRI/SNRI treatment using two different sets of response criteria (NeuroPharm and iSPOT-D). We replicated previous findings showing hyperstable EEG-wakefulness regulation in patients in comparison to healthy subjects. Responders defined by the iSPOT-D criteria showed a higher propensity toward low vigilance stages in comparison to patients with no response at pretreatment, however, this did not apply when using the NeuroPharm criteria. EEG-wakefulness regulation patterns normalized toward patterns of healthy controls after 8 weeks of treatment. This replication study supports the diagnostic value of EEG-vigilance regulation and its usefulness as a biomarker for the choice of treatment in MDD. • MDD show a more rigid vigilance regulation during rest compared to healthy control. • Patients with the hyperstable vigilance regulation profit less from escitalopram and duloxetine. • The wakefulness regulation of responders and remitters normalizes towards healthy controls after treatment. [ABSTRACT FROM AUTHOR]

Several electroencephalogram (EEG) biomarkers for prediction of drug response in major depressive disorder (MDD) have been proposed, but validations in larger independent datasets are missing. In the current study, we investigated the prognostic value of previously suggested EEG biomarkers. We gathered data that matched prior studies in terms of EEG methodology, clinical criteria for MDD, and statistical approach as closely as possible. The NeuroPharm study is a non-randomized and open label prospective clinical trial. One hundred antidepressant free patients with MDD were enrolled in the study and 79 (57 female) were included in the per-protocol analysis. The biomarkers candidates for cross-validation were derived from prior studies such as iSPOT-D and EMBARC and include frontal and occipital alpha power and asymmetry and delta and theta activity at anterior cingulate cortex (ACC). The alpha asymmetry, reported in two out of six prior studies, could be partially validated. We found that in female patients, larger right than left frontal alpha power prior to drug treatment was associated with better clinical outcome 8 weeks later. Moreover, female non-responder had higher central left alpha power relative to the right. In contrast to prior reports, we found that lower theta activity at ACC was present in remitters and was associated with greater improvement at week 8. We provide evidence that in women with MDD, alpha asymmetry seems to be the most promising EEG biomarker for prediction of treatment response. Registration number: NCT02869035. [ABSTRACT FROM AUTHOR]

• Pre-treatment reward fMRI evaluated in healthy and depressed individuals. • No difference in reward fMRI responses between healthy and depressed individuals. • Pre-treatment fMRI responses did not predict treatment response at eight weeks. • Treatment did not alter reward fMRI responses in depressed individuals. • These reward fMRI measures not supported as biomarkers of treatment response. Major depressive disorder (MDD) is a prevalent brain disorder for which anhedonia is a core symptom, indicating aberrations in the neural processing of reward. The striatum, medial prefrontal cortex (mPFC) and anterior insula (AI) are core reward processing regions. Here we used a reward-related, card-guessing functional magnetic resonance imaging (fMRI) paradigm to assay brain responses to reward in 90 MDD individuals and 58 healthy controls. We evaluated group differences in task-responsive, reward-related striatal, mPFC, and AI reactivity and whether baseline reactivity predicted an eight-week escitalopram antidepressant treatment response in MDD individuals. Thirty-eight MDD individuals also completed the reward paradigm after treatment and we evaluated antidepressant effects on reward reactivity estimates. Multivariate statistical analysis of task-responsive striatum, mPFC and AI brain responses did not reveal statistically significant differences between MDD and HC individuals (p uncorrected >0.23). Logistic regression models (five-fold cross-validation, statistical significance assessed with permutation testing) also did not support that baseline reward-related brain responses significantly predicted antidepressant treatment response (p uncorrected >0.39). Finally, reward-related brain responses were not statistically significantly changed over the course of treatment (p uncorrected >0.27). Our findings in a comparatively large MDD cohort do not support that these reward-related fMRI brain responses are informative biomarkers of MDD or antidepressant treatment response to escitalopram. [ABSTRACT FROM AUTHOR]