Major Depressive Disorder Adolescents Research Articles

Relationships between family functioning, parenting and peer victimization in adolescent depression: A cross-sectional study.

OBJECTIVE:Major depressive disorder (MDD) in adolescence is a prevalent mental health problem with a complex etiology and a rising incidence. The aim of the study investigated functioning of family, attitudes of parents, and peer victimization in adolescents with MDD and to compare those with healthy adolescents.METHODS:The study was designed as a multi-center, cross-sectional, case–control study. 98 adolescents diagnosed with MDD and 99 healthy controls were recruited for the study. Beck depression inventory, parental attitude research instrument (PARI) tool, family assessment device (FAD), and multidimensional peer victimization scale (MPVS) were applied to all participants. Descriptive, correlational, and bivariate group comparisons were used in analyses.RESULTS:The average ages of adolescents with MDD and control adolescents were 14.7 (S.D.=1.5) and 15.0 (S.D.=1.6) years, respectively. Females formed 74.5% of youth with MDD (vs. 70.3% of controls). The groups were similar in terms of socio-demographic features (all p>0.05). Adolescents with MDD had significantly elevated scores in FAD subscales except problem solving, PARI rejection of homemaking, marital conflict, and authoritarian subscales, and all MPVS subscales. Adolescents with MDD also displayed significant positive correlations between all MPVS subscales and FAD subscales except FAD problem-solving.CONCLUSION:This cross-sectional, multi-center study suggests that family dysfunction and peer victimization may be higher in youth with MDD. Although cross-sectional design precludes evaluation of causality, it may be prudent to evaluate family functions as well as peer victimization of depressed youth.

Alterations in the Levels of Growth Factors in Adolescents with Major Depressive Disorder: A Longitudinal Study during the Treatment with Fluoxetine.

Major depressive disorder (MDD) has a prevalence of 5% in adolescents. Several studies have described the association between the inflammatory response and MDD, but little is known about the relationship between MDD and growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF. It must be appointed that there are scarce reports on growth factors in adolescents with MDD and even fewer with a clinical follow-up. In this work, we evaluated the levels of growth factors (IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF) in MDD adolescents and the clinical follow-up during eight weeks of treatment with fluoxetine. Methods. All patients were diagnosed according to the DSM-IV-TR, and the severity of the symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS). Growth factors IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were quantified by cytometric bead array using serum samples from 22 adolescents with MDD and 18 healthy volunteers. Results. All patients showed clinical improvement since the fourth week of pharmacological treatment according to the HDRS. Considerably higher levels of IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were detected in MDD adolescents as compared to healthy volunteers. A significant but temporal decrease was detected in basic FGF, G-CSF, and GM-CSF at week four of fluoxetine administration. Conclusions. To the best of our knowledge, this is the first report to show alterations in the levels of growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF in MDD adolescents during eight weeks of clinical follow-up. These disturbances might be involved in the physiopathology of MDD since such growth factors have been proven to participate in the neural development and correct functioning of the CNS; therefore, subtle alterations in it may contribute to MDD.

Classifying Treated vs. Untreated MDD Adolescents from Anatomical Connectivity using Nonlinear SVM.

Identification of the treatment-related responders for adolescent Major Depressive Disorder (MDD) is urgently needed to develop effective treatments. In this paper, machine learning based classifiers are used to reveal anatomical features as responders for distinguishing MDD patients who have received treatment from those who never received any treatment. The features are drawn from two sets of measurements: 1) anatomical connectivity defined by diffusion tensor imaging measurements between a pair of brain regions, and 2) topological measurements from anatomical networks. Feature selection was performed based on p-value and minimum redundancy maximum relevance (mRMR) method to achieve improved classification accuracy. The classification performance is evaluated with a leave-one-out cross-validation method using 37 treated and 15 untreated subjects. The proposed methodology achieves 73% accuracy, 100% specificity, and 100% precision for 52 subjects. The most distinguishing features are the strength of the right hippocampus of the mean diffusivity (MD) network at 18% density and of the track-count (TR) network, the participation coefficient of the left middle temporal gyrus of the radial diffusivity (RD) network at 20% density, the axial diffusivity (AD) connectivity between right middle temporal gyrus and right supramarginal gyrus, the betweenness centrality of the right hippocampus of the TR network at 11% density, the apparent diffusion coefficient (ADC) connectivity between the left pars opercularis and the left rostral anterior cingulate cortex, the clustering coefficient of the middle anterior corpus callosum of the TR network at 11% density, and the AD connectivity between the left pars opercularis and the left rostral anterior cingulate cortex.

Abnormal changes of functional connectivity between anterior cingulate cortex and amygdala in adolescents patients with first-episode depression

Objective To study the resting-state functional connectivity(FC) changes of anterior cingulate cortex(ACC) and amygdala in adolescent patients with medication-naive first-episode major depressive disorder(MDD). Methods Medication-naive first-episode MDD adolescents(n=30) and pair-wise matched healthy controls(HCs, n=29) underwent resting-state functional magnetic resonance images(fMRI). To study whether there were different in FC changes between amygdala and ACC and whole brain regions, and whether abnormal FC was related to clinical characteristics. Results Compared with HCs, the adolescent MDD patients showed decreased FC between the left amygdala and right thalamus(MNI x, y, z: 15, -21, 18)(t=-2.85)and increased FC between the left amygdala and the bilateral temporal middle gyrus, left occipital gyrus, right medial prefrontal cortex(MPFC)(MNI x, y, z: 9, 66, 15)(t=2.80). The right amygdale showed decreased FC with bilateral middle frontal gyrus, left caudate(MNI x, y, z: -15, -9, 21)(t=-2.53), right thalamus(MNI x, y, z: 12, -36, 12)(t=-3.01), right cerebellum(MNI x, y, z: 3, -84, -33)(t=-2.45) and increased FC with right temporal middle gyrus, right MPFC(MNI x, y, z: 6, 69, 12)(t=2.41). The left ACC showed decreased FC with left cerebellum(MNI x, y, z: 12, -87, -24)(t=-2.36), left frontal inferior triangle gyrus, right frontal inferior orbital gyrus and increased FC with right frontal middle orbital gyrus.The right ACC showed decreased FC with left caudate(MNI x, y, z: -15, 21, 6)(t=-2.29), right temporal middle gyrus, right MPFC(MNI x, y, z: 9, 54, 36)(t=-2.29), right frontal inferior orbital gyrus, right angular(MNI x, y, z: 45, -51, 21)(t=-3.01), left dorsolateral prefrontal cortex(MNI x, y, z: -21, 33, 36)(t=-2.61). The increased FC between the left amygdale and bilateral temporal middle gyrus showed positive correlation with the score of HAMD(r=0.50, P<0.05; r=0.45, P<0.05). And the FC between the right amygdale and right middle frontal gyrus was positive correlation with duration of disease(r=0.63, P<0.05). Conclusion There is widespread FC disorder in amygdala and ACC in adolescents patients with first-episode depression.Abnormal FC changes may be the neuropathological mechanism of depression. Key words: Adolescent major depressive disorder; Resting-state fMRI; Functional connectivity; Amygdala; Anterior cingulated cortex

Effects of depressive disorders on quality of life perceptions among adolescents

Objective: In our study, the perception of quality of life in the adolescents diagnosed with major depressive disorder (MDD) was assessed by using multiple instruments to determine how their parents and adolescents were affected by depression in their own perspective, and the findings were compared with healthy control group. Thus, it is aimed to investigate the complementary nature of different types of instruments used in MDD during evaluation process by examining the relationship between depressive symptoms and quality of life. Methods: In our study, 38 adolescents diagnosed with MDD by using DSM-IV-TR criteria between 13 and 18 years old were recruited who admitted to or were already followed in Dokuz Eylul University (DEU) Child and Adolescents Psychiatry Department Outpatient Unit. Thirty-eight healthy controls between same age ranges with MDD adolescents were chosen from DEU’s catchment area. Both adolescents and their parents were asked to complete Turkish version of the Pediatric Quality of Life Inventory. A self-report inventory called Beck Depression Inventory (BDI) was used to assess depressive symptoms and a child psychiatrist fulfilled Clinic Global Impression-severity (CGI-S) and Children’s Global Assessment Scale (CGAS) forms for each participant. Result: It has been shown that comparing with healthy controls, MDD diagnosed children’s PedsQL total points and subtotal points were found statistically significantly lower. Adolescents diagnosed with MDD’s both PedsQL total and subtotal points were positively correlated with their parents. There were moderate relationship between both adolescents and their parents PedsQL points, self-report inventory called BDI and clinician rated CGAS and CGI-severity. Discussion: Our findings pointed out that because its descriptive features of experiencing subjective and environmental difficulties in functionality areas, PedsQL is one of the important instruments that supports clinical evaluation of severity of and impairment caused by depressive disorder.

Disrupted Structural and Functional Connectivity in Prefrontal-Hippocampus Circuitry in First-Episode Medication-Naïve Adolescent Depression.

BackgroundEvidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD). This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure.MethodsDiffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 26 first-episode medication-naïve MDD adolescents and 31 healthy controls (HC). Fractional anisotropy (FA) values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC) region showing significant differences between the two groups was identified.ResultsCompared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group.ConclusionsFirst-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD.

Altered neural function to happy faces in adolescents with and at risk for depression

BackgroundThere is accumulating evidence of alterations in neural circuitry underlying the processing of social-affective information in adolescent Major Depressive Disorder (MDD). However the extent to which such alterations are present in youth at risk for mood disorders remains unclear. MethodWhole-brain blood oxygenation level-dependent task responses and functional connectivity using generalized psychophysiological interaction (gPPI) analyses to mild and intense happy face stimuli was examined in 29 adolescents with MDD (MDD; M age, 16.0, S.D. 1.2 years), 38 healthy adolescents at risk of a mood disorder, by virtue of having a parent diagnosed with either Bipolar Disorder (BD) or MDD (Mood-risk; M age 13.4, S.D. 2.5 years) and 43 healthy control adolescents, having parents with no psychiatric disorder (HC; M age 14.6, S.D. 2.2 years). ResultsRelative to HC adolescents, Mood-risk adolescents showed elevated right dorsolateral prefrontal cortex (DLPFC) activation to 100% intensity happy (vs. neutral) faces and concomitant lowered ventral putamen activity to 50% intensity happy (vs. neutral) faces. gPPI analyses revealed that MDD adolescents showed significantly lower right DLPFC functional connectivity with the ventrolateral PFC (VLPFC) compared to HC to all happy faces. LimitationsThe current study is limited by the smaller number of healthy offspring at risk for MDD compared to BD. ConclusionsBecause Mood-risk adolescents were healthy at the time of the scan, elevated DLPFC and lowered ventral striatal activity in Mood-risk adolescents may be associated with risk or resiliency. In contrast, altered DLPFC–VLPFC functional connectivity in MDD adolescents may be associated with depressed mood state. Such alterations may affect social-affective development and progression to a mood disorder in Mood-risk adolescents. Future longitudinal follow-up studies are needed to directly answer this research question.

Neural Aspects of Inhibition Following Emotional Primes in Depressed Adolescents

Adults diagnosed with major depressive disorder (MDD) have been found to be characterized by selective attention to negative material and by impairments in their ability to disengage from, or inhibit the processing of, negative stimuli. Altered functioning in the frontal executive control network has been posited to underlie these deficits in cognitive functioning. We know little, however, about the neural underpinnings of inhibitory difficulties in depressed adolescents. We used functional magnetic resonance imaging in 18 adolescents diagnosed with MDD and 15 age- and gender-matched healthy controls (CTLs) while they performed a modified affective Go/No-Go task that was designed to measure inhibitory control in the presence of an emotional distractor. Participants were presented with either a happy or a sad face, followed by a go or a no-go target to which they either made or inhibited a motor response. A group (MDD, CTL) by valence (happy, sad) by condition (go, no-go) analysis of variance indicated that MDD adolescents showed attenuated BOLD response in the right dorsolateral prefrontal cortex (DLPFC) and in the occipital cortex bilaterally, to no-go targets that followed a sad, but not a happy, face. Adolescents diagnosed with MDD showed anomalous recruitment of prefrontal control regions during inhibition trials, suggesting depression-associated disruption in neural underpinnings of the inhibition of emotional distractors. Given that the DLPFC is associated with the maintenance of goal-relevant information, it is likely that sad faces differentially capture attention in adolescents with MDD and interfere with task demands requiring inhibition.

The neural correlates of emotional face-processing in adolescent depression: a dimensional approach focusing on anhedonia and illness severity

Deficits in emotion processing, a known clinical feature of major depressive disorder (MDD), have been widely investigated using emotional face paradigms and neuroimaging. However, most studies have not accounted for the high inter-subject variability of symptom severity. Similarly, only sparse research has focused on MDD in adolescence, early in the course of the illness. Here we sought to investigate neural responses to emotional faces using both categorical and dimensional analyses with a focus on anhedonia, a core symptom of MDD associated with poor outcomes. Nineteen medication-free depressed adolescents and 18 healthy controls (HC) were scanned during presentation of happy, sad, fearful, and neutral faces. ANCOVAs and regressions assessed group differences and relationships with illness and anhedonia severity, respectively. Findings included a group by valence interaction with depressed adolescents exhibiting decreased activity in the superior temporal gyrus (STG), putamen and premotor cortex. Post-hoc analyses confirmed decreased STG activity in MDD adolescents. Dimensional analyses revealed associations between illness severity and altered responses to negative faces in prefrontal, cingulate, striatal, and limbic regions. However, anhedonia severity was uniquely correlated with responses to happy faces in the prefrontal, cingulate, and insular regions. Our work highlights the need for studying specific symptoms dimensionally in psychiatric research.

Multilevel assessment of the neurobiological threat system in depressed adolescents: interplay between the limbic system and hypothalamic-pituitary-adrenal axis.

Integrative, multilevel approaches investigating neurobiological systems relevant to threat detection promise to advance understanding of the pathophysiology of major depressive disorder (MDD). In this study we considered key neuronal and hormonal systems in adolescents with MDD and healthy controls (HC). The goals of this study were to identify group differences and to examine the association of neuronal and hormonal systems. MDD and HC adolescents (N = 79) aged 12-19 years were enrolled. Key brain measures included amygdala volume and amygdala activation to an emotion face-viewing task. Key hormone measures included cortisol levels during a social stress task and during the brain scan. MDD and HC adolescents showed group differences on amygdala functioning and patterns of cortisol levels. Amygdala activation in response to emotional stimuli was positively associated with cortisol responses. In addition, amygdala volume was correlated with cortisol responses, but the pattern differed in depressed versus healthy adolescents, most notably for unmedicated MDD adolescents. The findings highlight the value of using multilevel assessment strategies to enhance understanding of pathophysiology of adolescent MDD, particularly regarding how closely related biological threat systems function together while undergoing significant developmental shifts.

Cortical thickness in youth with major depressive disorder

BackgroundStudies in adults with major depressive disorder (MDD) have implicated dysregulation of frontal-limbic circuits in the symptomology of this disorder. We hypothesized that the middle frontal gyrus (MFG; a core portion of the dorsolateral prefrontal cortex or DLPFC) and the anterior cingulate (caudal), regions implicated in emotive and cognitive control, would display a reduced cortical thickness in youth with MDD as compared to healthy, non-depressed adolescents.MethodsSixteen healthy control adolescents (17.19 ± 1.87 years; 7 males, 9 females) and thirty MDD participants (16.89 ± 2.01 years; 9 males, 21 females) underwent magnetic resonance imaging (MRI). Cortical thickness analysis was carried out using FreeSurfer software.ResultsCounter to our hypothesis, we observed thicker right and left rostral MFG in MDD adolescents as compared to controls (p = 0.004 and p = 0.005, respectively). Furthermore, the left caudal anterior cingulate cortex was thicker in MDD subjects as compared to controls (p = 0.009). In MDD subjects, there was a significant inverse correlation between age and left MFG thickness (r = -0.45, p = 0.001).ConclusionsThese results have implications for the developmental trajectory of the frontal lobe in adolescent MDD. The MFG is implicated in the frontal-limbic circuits underlying executive functioning and their interaction with affective processing. Alterations in this region are likely involved with the symptoms of MDD. Limitations include a small sample size and cross sectional design.

White matter abnormalities in adolescents with major depressive disorder

The purpose of this study was to identify areas of abnormal white matter microstructure in adolescents with Major Depressive Disorder (MDD) using diffusion tensor imaging (DTI). Fractional anisotropy (FA) values representing preferential diffusivity along major tracts were examined using tract-based spatial statistics across the whole brain in adolescents ages 13-19 with MDD (n = 31) compared with demographically-matched healthy controls (n = 31). We not only examined frontal lobe tracts that have been most frequently identified as abnormal in previous DTI studies of older depressed patients, but also tested for FA group differences across the whole brain to determine if adolescent depression was related to any other regional white matter abnormality. MDD-diagnosed adolescents had significantly lower FA in many regions concentrated predominantly in the frontal lobe. There also was strong evidence for lower FA in bilateral anterior/posterior limbs of the internal capsules, as well as tracts through the midbrain, left external capsule, right thalamic radiation and left inferior longitudinal fasciculus. Consistent with previous findings in depressed young and elderly adults, the current study found evidence for abnormal microstructure in white matter connections of the frontal lobe in MDD adolescents. There also was strong evidence for FA abnormalities in corpus callosum genu, internal and external capsule tracts, thalamus and midbrain, notable for both the relative magnitude of these effects and absence from most previous white matter studies of depression. These abnormalities might represent important markers of early life-onset depression.

Functional connectivity of negative emotional processing in adolescent depression

BackgroundThe subgenual anterior cingulate cortex (sgACC) and its connected circuitry have been heavily implicated in emotional functioning in adolescent-onset major depressive disorder (MDD). While several recent studies have examined sgACC functional connectivity (FC) in depressed youth at rest, no studies to date have investigated sgACC FC in adolescent depression during negative emotional processing. MethodsNineteen medication-naïve adolescents with MDD and 19 matched healthy controls (HCL) performed an implicit fear facial affect recognition task during functional magnetic resonance imaging (fMRI). We defined seeds in bilateral sgACC and assessed FC using the psychophysiological interaction method. We also applied cognitive behavioral modeling to estimate group differences in perceptual sensitivity in this task. Finally, we correlated connectivity strength with clinical data and perceptual sensitivity. ResultsDepressed adolescents showed increased sgACC-amygdala FC and decreased sgACC-fusiform gyrus, sgACC-precuneus, sgACC-insula, and sgACC-middle frontal gyrus FC compared to HCL (p<0.05, corrected). Among the MDD, sgACC-precuneus FC negatively correlated with depression severity (p<0.05, corrected). Lastly, MDD adolescents exhibited poorer perceptual sensitivity in the task than HCL, and individual differences in perceptual sensitivity significantly correlated with sgACC FC and depression scores (p<0.05, corrected). LimitationsSubjects were clinically homogenous, possibly limiting generalizability of the findings. ConclusionsAdolescent depression is associated with biased processing of negative stimuli that may be driven by sgACC dysregulation and may possibly lead to an imbalance among intrinsic functional brain networks. This work also establishes the use of combining neuroimaging and cognitive behavioral modeling methods to investigate cognitive and neural differences between psychiatric and healthy populations.

Fronto-Striato-Cerebellar Dysregulation in Adolescents with Depression During Motivated Attention

Pediatric major depressive disorder (MDD) is associated with deficits in sustained attention, thought to be related to underlying motivation deficits. This hypothesis, however, has never directly been tested using functional magnetic resonance imaging. In this study, we investigated the neurofunctional correlates of the interplay between attention and motivation in medication-naive pediatric MDD using a rewarded sustained attention task. Functional magnetic resonance imaging was used to compare brain activation between 20 medication-naïve, noncomorbid, first-episode adolescents with MDD aged 13 to 18 years and 21 gender-, age-, and IQ-matched healthy adolescents. Participants performed a sustained attention task with and without a monetary reward to assess the impact of reward on sustained attention networks. During nonrewarded sustained attention, adolescents with MDD showed reduced activation compared with healthy control subjects in occipital cortex. When sustained attention was rewarded, however, the underactivation in adolescents with MDD was in an extensive right hemispheric network of inferior fronto-striato-thalamic attention and limbic hippocampus-anterior cingulate reward processing areas. Major depressive disorder patients showed increased activation in cerebellum, which correlated with reduced frontal activation and depressive symptoms, suggesting compensatory response. Further analysis showed that reward upregulated fronto-striatal and hippocampal/temporal activation in control subjects but deactivated these regions in MDD, with opposite effects in the cerebellum. Medication-naïve MDD adolescents show abnormalities in the regulation in fronto-striato-cerebellar brain regions involved in attention and reward during motivated but not unmotivated attention. This suggests a dysfunctional interplay between motivation and cognition in pediatric MDD, where motivation appears less capable of upregulating attention networks relative to healthy youths.

Increased Activity Imbalance in Fronto-Subcortical Circuits in Adolescents with Major Depression

BackgroundA functional discrepancy exists in adolescents between frontal and subcortical regions due to differential regional maturational trajectories. It remains unknown how this functional discrepancy alters and whether the influence from the subcortical to the frontal system plays a primacy role in medication naïve adolescent with major depressive disorder (MDD).Methodology/Principal FindingsEighteen MDD and 18 healthy adolescents were enrolled. Depression and anxiety severity was assessed by the Short Mood and Feeling Questionnaire (SMFQ) and Screen for Child Anxiety Related Emotional Disorders (SCARED) respectively. The functional discrepancy was measured by the amplitude of low-frequency fluctuations (ALFF) of resting-state functional MRI signal. Correlation analysis was carried out between ALFF values and SMFQ and SCARED scores. Resting brain activity levels measured by ALFF was higher in the frontal cortex than that in the subcortical system involving mainly (para) limbic-striatal regions in both HC and MDD adolescents. The difference of ALFF values between frontal and subcortical systems was increased in MDD adolescents as compared with the controls.Conclusions/SignificanceThe present study identified an increased imbalance of resting-state brain activity between the frontal cognitive control system and the (para) limbic-striatal emotional processing system in MDD adolescents. The findings may provide insights into the neural correlates of adolescent MDD.

The kynurenine pathway in adolescent depression: Preliminary findings from a proton MR spectroscopy study

Cytokine induction of the enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in the development of major depressive disorder (MDD). IDO metabolizes tryptophan (TRP) into kynurenine (KYN), thereby decreasing TRP availability to the brain. KYN is further metabolized into several neurotoxins. The aims of this pilot were to examine possible relationships between plasma TRP, KYN, and 3-hydroxyanthranilic acid (3-HAA, neurotoxic metabolite) and striatal total choline (tCho, cell membrane turnover biomarker) in adolescents with MDD. We hypothesized that MDD adolescents would exhibit: i) positive correlations between KYN and 3-HAA and striatal tCho and a negative correlation between TRP and striatal tCho; and, ii) the anticipated correlations would be more pronounced in the melancholic subtype group. Fourteen adolescents with MDD (seven with melancholic features) and six healthy controls were enrolled. Minimums of 6 weeks MDD duration and a severity score of 40 on the Children's Depression Rating Scale-Revised were required. All were scanned at 3T with MRI, multi-voxel 3-dimensional, high, 0.75 cm(3), spatial resolution proton magnetic resonance spectroscopic imaging. Striatal tCho concentrations were assessed using phantom replacement. Spearman correlation coefficients were Bonferroni-corrected. Positive correlations were found only in the melancholic group, between KYN and 3-HAA and tCho in the right caudate (r=0.93, p=0.03) and the left putamen (r=0.96, p=.006), respectively. These preliminary findings suggest a possible role of the KYN pathway in adolescent melancholic MDD. Larger studies should follow.

A preliminary study of functional connectivity in comorbid adolescent depression

Major depressive disorder (MDD) begins frequently in adolescence and is associated with severe outcomes, but the developmental neurobiology of MDD is not well understood. Research in adults has implicated fronto-limbic neural networks in the pathophysiology of MDD, particularly in relation to the subgenual anterior cingulate cortex (ACC). Developmental changes in brain networks during adolescence highlight the need to examine MDD-related circuitry in teens separately from adults. Using resting state functional magnetic resonance imaging (fMRI), this study examined functional connectivity in adolescents with MDD ( n = 12) and healthy adolescents ( n = 14). Seed-based connectivity analysis revealed that adolescents with MDD have decreased functional connectivity in a subgenual ACC-based neural network that includes the supragenual ACC (BA 32), the right medial frontal cortex (BA 10), the left inferior (BA 47) and superior frontal cortex (BA 22), superior temporal gyrus (BA 22), and the insular cortex (BA 13). These preliminary data suggest that MDD in adolescence is associated with abnormal connectivity within neural circuits that mediate emotion processing. Future research in larger, un-medicated samples will be necessary to confirm this finding. We conclude that hypothesis-driven, seed-based analyses of resting state fMRI data hold promise for advancing our current understanding of abnormal development of neural circuitry in adolescents with MDD.

Depression, suicidal behavior and insight in adolescents with schizophrenia

To investigate the interrelationships between depressive symptoms of adolescent schizophrenia, post-psychotic depression (PPD), negative signs, suicidal behavior and insights into the disease. Three groups of 16 adolescent inpatients were assessed with regard to: Schizophrenia alone, schizophrenia with PPD and major depressive disorder (MDD). The following measures were used: DSM IV diagnostic criteria, the Calgary Depression Scale for Schizophrenia (CDSS), the PANSS (Positive and Negative Signs of Schizophrenia Scale), (BDI) Beck Depression Inventory, (CCL) Cognitive Check List, (HS) Hopelessness Scale, (SRS) Suicide Risk Scale, (CSPS) Child Suicide Potential Scale and the (SAUMD) Scale to Assess Unawareness of Mental Disorder. Compared with MDD adolescents, PPD adolescents showed few somatic and behavioral symptoms of depression but had equally severe cognitive and affective depressive symptomatology. Suicide risk scores and actual suicidal behavior was prominent in PPD adolescents. A positive and significant correlation was found between PPD symptoms, suicide risk and awareness of disease (insight). Negative symptoms of schizophrenia could be distinguished from PPD symptoms and there was a negative correlation between blunted affect and PPD scores. PPD can be diagnosed in adolescent schizophrenia. The symptom pattern is different from MDD, therefore, there may be cause to modify DSM IV provisional criteria for this condition. Adolescents with schizophrenia who have insight into their illness are at higher risk for suicidal behavior and the development of PPD.

Major depressive disorder in adolescents: Family psychiatric history predicts severe behavioral disinhibition

Background Major Depressive Disorder (MDD) becomes increasingly prevalent during adolescence and is associated with substantial psychiatric comorbidity and psychosocial impairment. The marked behavioral heterogeneity evident among adolescents with MDD suggests the possibility of distinct subtypes. This study was designed to determine whether family psychiatric histories differ between groups of MDD adolescents defined by the presence or absence of severe behavioral disinhibition. Methods Adolescents with MDD ( n = 71) completed the Buss–Durkee Hostility Inventory—Adapted, Adolescent Aggressive Incidents Interview (AAII), Measure of Aggression, Violence, and Rage in Children, Diagnostic Interview Schedule for Children, Suicidal Ideation Questionnaire-JR., Suicidal Behavior Inventory, and Reynolds Adolescent Depression Scale. Parents completed the Family Informant Schedule and Criteria, Children's Affective Liability Scale, AAII, and a partial DISC. Behavioral disinhibition (BD) measures were used to assign adolescents to MDD + BD ( n = 41) and MDD − BD ( n = 30) groups. Results The MDD + BD group had a higher prevalence of drug use disorders in biological fathers than the MDD − BD group. The MDD + BD group also had higher proportions of paternal second degree relatives with alcohol use disorders, drug use disorders, and psychiatric hospitalizations, and a higher proportion of maternal second degree relatives with antisocial personality disorder. Limitations Limitations include reliance on single informants for family psychiatric histories and the failure to distinguish between child- and adolescent-onset depression. Conclusions Family psychiatric histories differentiated MDD adolescents grouped by the presence or absence of behavioral disinhibition, suggesting possible etiologic mechanisms. Further research on subtypes or comorbid presentations may assist in the development of targeted treatment strategies.

Clinical features of major depressive disorder in adolescents and their relatives: Impact on familial aggregation, implications for phenotype definition, and specificity of transmission.

Three questions were addressed using family study data from a community sample: (a) Which clinical features of major depressive disorder (MDD) in adolescents are associated with elevated rates of MDD in relatives? (b) Which features of MDD in relatives distinguish family members of depressed adolescents from relatives of adolescents without mood disorders (NMD)? and (c) Do depressed adolescents with particular features have higher proportions of depressed relatives with the same features? Participants included 268 MDD adolescents, 401 NMD adolescents, and their 2,202 first-degree relatives. Rates of MDD were highest among relatives of depressed adolescents with recurrent episodes and greater impairment. Depression severity best distinguished the relatives of depressed adolescents from relatives of controls. Specific clinical features did not aggregate in families.