Intranasal esketamine as therapeutic option: a case report of an adolescent with treatment resistant depression

Depression is among the most common mental health disorders worldwide and treatment resistant depression (TRD) represents a major challenge for both patients and clinicians. In recent years ketamine has received attention as an antidepressant agent, demonstrating promising results in TRD in adults. To date, few attempts have been made in treating adolescent TRD with ketamine and none have used intranasal application. This paper discusses a case of a 17-year-old female adolescent suffering from TRD who underwent treatment with intranasal esketamine application (Spravato 28 mg). As symptoms showed clinically insignificant improvement despite modest gains in objective assessments (GAF, CGI, MADRS), treatment was prematurely discontinued. However, the treatment was tolerable and side effects were scarce and mild. Although this case report does not demonstrate clinical effectiveness, ketamine may nonetheless be a promising substance in treating TRD in other adolescents. Questions regarding the safety of ketamine use in the rapidly developing brains of adolescents still remain unanswered. To further explore the potential benefits of this treatment method a short term RCTs for adolescents with TRD is recommended

Differential neural processing of social exclusion in adolescents with non-suicidal self-injury: An fMRI study

AbstractNon-suicidal self-injury (NSSI) is highly prevalent in adolescence and has been suggested as an autonomous diagnosis in the Diagnostic and Statistical Manual (DSM-5). Social rejection is as potential risk-factor for NSSI and depression in adolescence. Objectives of this study were to identify differences in neural processing of social rejection in depressed adolescents with and without co-morbid NSSI and healthy controls. Participants were 28 depressed adolescents (14 with co-morbid NSSI, 79% females) and 15 healthy controls, with an average age of 15.2 years (SD=1.8). Social exclusion was implemented using the Cyberball paradigm ‘Cyberball’ during functional magnetic resonance imaging (fMRI). All participants reported feelings of social exclusion after fMRI scanning. Investigating the effects of NSSI, we found that depressed adolescents with NSSI showed relatively enhanced activation of the medial prefrontal cortex (mPFC) and the ventrolateral prefrontal cortex (vlPFC) compared to depressed adolescents without NSSI and also compared to healthy controls. Results point towards divergent processing of social exclusion in depressed adolescents with NSSI as compared to adolescents with mere depression in brain regions previously related to the processing of social exclusion. This finding of distinct neurophysiological responses may stimulate further research on individual treatment approaches

The situation of former adolescent self-injurers as young adults: a follow-up study

Background: Nonsuicidal self-injury (NSSI) in adolescence has been described as comorbid condition in affective or anxiety disorders, as well as borderline personality disorder (BPD) and is a risk factor for later suicide attempts. Prevalence rates of NSSI decline steeply from adolescence to young adulthood. Yet, to the best of our knowledge, the longitudinal development of adolescent psychiatric patients with NSSI into their young adulthood has not been investigated. The aim of this study was to assess current NSSI and psychological impairment of young adults, who had been in treatment for NSSI in their adolescence. Methods: Former patients of the departments of child and adolescent psychiatry and psychotherapy in Ulm and Ravensburg, Germany (N = 52), who presented with NSSI in their adolescence, were recruited (average age: 21.5 years (SD = 2.6)). Data was assessed using questionnaires and structured clinical interviews. Two groups of participants with prevailing NSSI and ceased NSSI were compared concerning their current psychological impairment, history of NSSI, suicide attempts, and BPD diagnosis. Results: Around half of all participants had engaged in NSSI within the last year, and around half met diagnostic criteria for BPD. Although there was no significant association between current NSSI and BPD, an earlier age of onset of NSSI and a longer duration of NSSI during adolescence was significantly predictive of adult BPD. Two thirds of participants still met criteria of an axis 1 psychiatric disorder. Suicide attempts were reported by 53.8 % of all participants. Participants with current NSSI were more likely to meet criteria for a current axis 1 disorder, had engaged in NSSI more often in their lifetime, and reported more suicide attempts. Conclusions: Reduction of NSSI from adolescence to young adulthood was lower than described in previous community samples. This may be due to the initial high psychiatric impairment of this sample in adolescence. Early onset of NSSI seemed to be a risk factor for a longer duration of NSSI during adolescence but not for NSSI prevailing into adulthood. However, it was a risk factor for adult BPD. Furthermore, the occurrence of suicidal thoughts and behaviors and prevailing NSSI was highly associated

Somatosensory Stimulus Intensity Encoding in Borderline Personality Disorder

Borderline Personality Disorder (BPD) is clinically characterized by emotional instability, interpersonal disturbances and dysfunctional behavior such as non-suicidal self-injury (NSSI). During NSSI, patients with BPD typically report analgesic or hypoalgesic phenomena, and pain perception and pain processing in BPD have been repeatedly investigated. Most of the studies so far focused on affective-motivational and cognitive-evaluative neural components of pain within categorial study designs. By contrast, rather basic somatosensory aspects such as neural intensity-encoding of somatosensory stimuli were not examined in further details. Thus, we investigated patients with BPD and healthy controls (HC) by functional magnetic resonance imaging (fMRI) during an unpleasant sensory stimulation task with parametrically increasing stimulus intensities. 15 females diagnosed with BPD and 15 HCs were investigated with fMRI during four individually adjusted levels of electrical stimulus intensities. Ratings of stimulus intensity were assessed by button presses during fMRI. fMRI-data were analyzed by analyses of variances (ANOVA) at a statistical threshold of p < 0.05 FWE-corrected on cluster level. Subjective ratings of stimulus intensities were alike between BPD and HC, and intensity levels identified with equal accuracy. Significant intensity-encoding neural activations were observed within the primary and secondary somtasensory cortex, the posterior insula, the posterior midcingulate cortex (pMCC) and the supplementary motor area (SMA) in both, HC and BPD. Notably, there were no significant between-groups differences in intensity-encoding neural activations, even at lowered significance thresholds. Present results suggest a similar neural somatosensory stimulus intensity encoding in BPD as previously observed on a behavioral level. The alterations in neural affective-motivational or cognitive-evaluative components reported so far may be restricted to pain rather than unpleasant stimulus processing and were absent in our study

The Interplay between Child Maltreatment and Stressful Life Events during Adulthood and Cardiovascular Problems—A Representative Study

Psychological stress is a major risk factor for cardiovascular diseases. While the relevance of early life stress, such as that which is due to child maltreatment (CM), is well known to impact individual stress responses in the long-term, and data on the interplay between CM and stressful events in adulthood on cardiovascular health are sparse. Here, we aimed to assess how stressful life events in adulthood are associated with cardiovascular health infarction in later life and whether this association is independent of CM. In a cross-sectional design, a probability sample of the German population above the age of 14 was drawn using different sampling steps. The final sample included 2510 persons (53.3% women, mean age: 48.4 years). Participants were asked about sociodemographic factors, adult life events, CM, and health conditions in adulthood. Results indicate that the number of experienced adverse life events in adulthood is associated with significantly increased odds for obesity (Odds Ration (OR)women = 1.6 [1.3; 2.0], ORmen = 1.4 [1.1; 1.9]), diabetes (ORwomen = 1.5 [1.1; 2.1], ORmen = 1.5 [1.1; 2.3]) and myocardial infarction (ORwomen = 2.1 [1.0; 4.3], ORmen = 1.8 [1.1; 2.8]). This association is not moderated by the experience of CM, which is associated with cardiovascular problems independently. Taken together, adult stressful life events and CM are significantly and independently associated with cardiovascular health in men and women in the German population in a dose-dependent manner. General practitioners, cardiologists and health policy-makers should be aware of this association between psychosocial stressors during childhood and adulthood and cardiovascular health

Neural Correlates of Social Inclusion in Borderline Personality Disorder

Humans engage in social interactions and have a fundamental need and motivation to establish and maintain social connections. Neuroimaging studies particularly focused on the neural substrates of social exclusion in healthy subjects (HC), borderline personality disorder (BPD), and major depression (MD). However, there is evidence regarding neural alterations also during social inclusion in BPD that we intended to elucidate in our study. Considering that patients with BPD often have comorbid MD, we investigated patients with BPD, and comorbid MD, patients with MD without BPD, and a sample of HC. By investigating these two clinical samples within one study design, we attempted to disentangle potential confounds arising by psychiatric disorder or medication and to relate neural alterations under social inclusion specifically to BPD. We investigated 48 females (15 BPD and MD, 16 MD, and 17 HC) aged between 18 and 40 years by fMRI (3T), using the established cyberball paradigm with social exclusion, inclusion, and passive watching conditions. Significant group-by-condition interaction effects (p < 0.05, FWE-corrected on cluster level) were observed within the dorsolateral (dlPFC) and dorsomedial prefrontal cortex (dmPFC), the temporo-parietal junction (TPJ), the posterior cingulate cortex (PCC), and the precuneus. Comparisons of estimated neural activations revealed that significant interaction effects were related to a relative increase in neural activations during social inclusion in BPD. In detail, we observed a significant increase in differential (social inclusion vs. passive watching) neural activation within the dmPFC and the PCC in BPD compared to both, MD and HC. However, significant interaction effects within the dlPFC and the TPJ could not specifically be linked to BPD considering that they did not differ significantly between the two clinical groups in post-hoc comparisons. Our study supports previous results on effects of social and inclusion in BPD, and provides further evidence regarding disorder specific neural alterations in BPD for brain regions associated with self-referential and mentalizing processes during social inclusion

Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity

Background: The term ‘self-harm’ encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as ‘Alternative’ (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as ‘Jocks’ are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group ‘bonding’) functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.<p></p> Methods: An anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).<p></p> Results: An “Alternative” identity was directly (r ≈ 0.3) and a “Jock” identity inversely (r ≈ -0.1) correlated with self-harm. “Alternative” teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4–8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.<p></p> Conclusions: About half of ‘Alternative’ adolescents’ self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. ‘To feel more a part of a group’