Full Remission Research Articles

Citalopram-induced pathways regulation and tentative treatment-outcome-predicting biomarkers in lymphoblastoid cell lines from depression patients

Antidepressant therapy is still associated with delays in symptomatic improvement and low response rates. Incomplete understanding of molecular mechanisms underlying antidepressant effects hampered the identification of objective biomarkers for antidepressant response. In this work, we studied transcriptome-wide expression followed by pathway analysis in lymphoblastoid cell lines (LCLs) derived from 17 patients documented for response to SSRI antidepressants from the Munich Antidepressant Response Signatures (MARS) study upon short-term incubation (24 and 48 h) with citalopram. Candidate transcripts were further validated with qPCR in MARS LCLs from responders (n = 33) vs. non-responders (n = 36) and afterward in an independent cohort of treatment-resistant patients (n = 20) vs. first-line responders (n = 24) from the STAR*D study. In MARS cohort we observed significant associations of GAD1 (glutamate decarboxylase 1; p = 0.045), TBC1D9 (TBC1 Domain Family Member 9; p = 0.014–0.021) and NFIB (nuclear factor I B; p = 0.015–0.025) expression with response status, remission status and improvement in depression scale, respectively. Pathway analysis of citalopram-altered gene expression indicated response-status-dependent transcriptional reactions. Whereas in clinical responders neural function pathways were primarily up- or downregulated after incubation with citalopram, deregulated pathways in non-responders LCLs mainly involved cell adhesion and immune response. Results from the STAR*D study showed a marginal association of treatment-resistant depression with NFIB (p = 0.068) but not with GAD1 (p = 0.23) and TBC1D9 (p = 0.27). Our results propose the existence of distinct pathway regulation mechanisms in responders vs. non-responders and suggest GAD1, TBC1D9, and NFIB as tentative predictors for clinical response, full remission, and improvement in depression scale, respectively, with only a weak overlap in predictors of different therapy outcome phenotypes.

Antineutrophil Cytoplasmic Antibodies Negative Microscopic Polyangiitis With Initial Pulmonary Manifestation

Microscopic polyangiitis (MPA) is a small vessel vasculitides mostly associated with anti-neutrophil cytoplasmic antibodies (ANCA). The kidney is the most commonly affected organ in MPA. We report the case of a 9-year-old girl with ANCA-negative MPA who initially presented with respiratory symptoms, including cough, sputum, and dyspnea. Based on her symptoms, atypical pneumonia was suspected. Also, childhood interstitial lung disease was considered based on findings seen on chest CT. Despite initial improvement of symptoms with oral corticosteroid therapy, dyspnea with initiation of corticosteroid tapering was noted. A final diagnosis of MPA was made after lung biopsy. ANCA was negative in both the initial and repeat blood tests. Oral cyclophosphamide and prednisolone treatments led to full remission. Since then, the patient has been treated with low dose prednisolone and azathioprine for maintenance. A good treatment response was achieved and her clinical symptoms, pulmonary functions, and radiologic findings have since improved. Thus, early and precise diagnosis of MPA is crucial for remission induction and prevention of symptom relapse. (J Rheum Dis 2020;27:203-208)

Postpartum psychosis: can it be prevented? A high-risk case report with a favorable outcome

Introduction: postpartum psychosis is a rare psychiatric emergency that poses serious risks to both mother and child. Suicide and infanticide are the worst outcomes. Perinatal clinical and psychiatric examination is crucial in order to determine which patients are at high risk. Case Report: A puerperal patient whose 23-day-old son was a wanted child from a planned pregnancy presented with behavioral changes that began seventeen days after the birth, including introversion, incoherent speech, soliloquy, and auditory hallucinations. She was into one of psychomotor agitation, irritability, and disorganized and hazardous behavior. At the diagnosis, she was suffering delusions of guilt and unfaithfulness. She was paranoid and negligent with her newborn. Previous psychiatric events appeared to be a manic episode. Pharmacological treatment resulted in full remission, and she was discharged from hospital. Discussion: This condition is frequently overlooked due to its low incidence. This case report are suggestive of the need for greater observance during the perinatal period. Red flags include history of post-partum psychosis or bipolar disorder, clinical prodromal signs such as delirium, psychomotor agitation, and mental confusion, especially when social stress factors are present. Conclusion: A thorough medical evaluation is recommended in order to prevent risks and implement preventative treatment, such as Lithium Carbonate.

Near-infrared phototherapy for patient-derived orthotopic xenograft model of hepatocellular carcinoma in combination with indocyanine green

BackgroundHepatocellular carcinoma notably takes up and retains indocyanine green (ICG). Here, we investigated whether patient-derived orthotopic xenograft of hepatocellular carcinoma could accumulate ICG and show full remission via phototherapy. MethodsNIR light and ICG were tested for cytotoxicity in cancerous cell lines (Huh-7, Hep3B). Patient-derived orthotopic xenograft (PDoX) mice were subjected to phototherapy comprising of daily NIR exposure (0.5–1.75 W/cm2) and intravenous injection of ICG (5–20 mg/kg2). Moreover, NIR laser was flashed on individual mouse until hepatocellular carcinoma completely loss the fluorescence, as determined by NIR camera. ResultsCytotoxicity increased in response to the input energy, but insufficient energy (< 150 joule/cm2) was irresponsive at all irradiances. NIR irradiance in the range of 0.5–1.75 W/cm2 took 5–7 days to elicit complete remission from PDoX mice in combination with 20 mg/kg ICG. In contrast, phototherapy could completely ablate hepatocellular carcinoma at 5–15 mg/kg ICG. ConclusionsICG could potentiate the tumoricidal ability of NIR light in a dose-dependent manner, and vice versa. Regardless of ICG dosage, however, phototherapy treated group showed a relatively high survival rate compared to the non-treated group. Notably, real-time phototherapy could halve the effective ICG dosage for full remission of deep-seated tumor.

Von Hippel–Lindau disease with concomitant Hodgkin’s disease and congenital hypertrophy of the retinal pigment epithelium

The article presents a rare case of combination of von HippelLindau disease and Hodgkins disease. The disease began with neurological symptoms with gradual progression over the next 3 years. The diagnosis of von HippelLindau disease was made after MRI of brain and spinal cord, abdominal MICTs, and detection of brain stem and spinal cord tumors, multiple pancreatic cysts. We performed resection trepanation of the posterior cranial fossa and microsurgical total removal of hemangioblastoma of the medulla oblongata. After 1.5 years the patient is diagnosed with Hodgkins disease and several courses of chemotherapy are carried out, reaching full remission, confirmed by PET with CT. 14 months later, the patient consulted an ophthalmologist due to visual impairment and floating opacities in her left eye. The ophthalmologic examination for the first time revealed multiple bilateral retinal hemangiomas and vitreal hemorrhages from tractional retinal tears caused by posterior hyaloid detachment and unrelated to hemangiomas in the left eye. The barrier laser coagulation of the left eye retinal tears was performed, and the observation tactics was adopted.

Recommendations for treating life-threatening Kaposi sarcoma during pregnancy in HIV-positive women in low income countries.

In areas of high HIV and human herpes virus 8 prevalence, life-threatening forms of Kaposi sarcoma (KS) can occur in HIV-positive women during pregnancy. Treating KS in pregnancy must balance both the well-being of the mother with the health of the fetus, yet data and recommendations on the best treatment approach for KS during pregnancy are limited. Without effective treatment, which can be difficult to obtain in low income countries (LICs), the mother and infant are at risk for poor outcomes. A successful case report is used as teaching example, followed by a detailed review of the literature that culminates in recommendations for treating KS during pregnancy among HIV-positive women in LICs. A 31-year-old HIV-positive woman presented for care in April 2016 at 28 weeks gestation with extensive KS skin lesions, KS lymphadenopathy, and a large oropharynx KS lesion causing partial airway obstruction. She had initiated antiretroviral therapy (ART) months prior and was virally suppressed, suggesting KS-immune reconstitution inflammatory syndrome. Due to the severity of KS and her third trimester status, combination chemotherapy was initiated using bleomycin, vincristine, and doxorubicin followed by maintenance therapy with paclitaxel. She showed remarkable response to the chemotherapy and had a normal vaginal delivery of a healthy baby at full term. Full clinical remission was achieved, and her baby was HIV-negative with no negative health effects of the KS or the chemotherapy. Review of the sparse existing literature demonstrates the importance, safety, and effectiveness of treating KS during pregnancy. We offer simple adaptable treatment recommendations for use in treating HIV-positive women with KS during pregnancy in LICs. Life-threatening KS can be treated using chemotherapy and ART in resource-limited settings, allowing for good outcomes in mother and infant. While monotherapy with liposomal doxorubicin or paclitaxel is preferred, these are often not available in LICs. As alternatives, bleomycin, vincristine, and doxorubicin can be safely used during the second and/or third trimesters for treating KS. Following a simple treatment approach can be an effective way to treat KS in pregnancy for pregnant women living with HIV in an LIC setting.

Sleep and physical activity in patients with newly diagnosed bipolar disorder in remission, their first-degree unaffected relatives and healthy controls

BackgroundSleep disturbances are a central feature in bipolar disorder (BD) that often persist in remission and seem to be present also in unaffected first-degree relatives (UR) of patients with BD, presenting a possible risk factor for later onset of BD. However, it is unknown if these disturbances are associated with unhealthy life-style as reflected in low levels of physical activity. We investigated sleep disturbances and physical activity levels in patients with newly diagnosed BD in full or partial remission, their UR and healthy controls (HC).MethodsSleep patterns and physical activity were compared in 227 patients with newly diagnosed BD, 76 UR and 148 HC. The Pittsburgh Sleep Quality Index (PSQI) and the International Physical Activity Questionnaire (IPAQ) were used to assess sleep disturbances and physical activity, respectively.ResultsIn sex- and age-adjusted analyses, patients with BD exhibited more sleep disturbances and lower physical activity compared with UR and HC, respectively. Unaffected relatives reported significantly longer sleep latency and a non-significant trend towards more overall sleep disturbances compared with HC.ConclusionsSleep disturbances and less physical activity are present in patients with newly diagnosed BD in partial or full remission. Individuals at familiar risk of BD reported longer sleep latency and similar physical activity compared with HC. Further prospective studies are needed to clarify whether these discrete sleep disturbances act as risk factor for later onset of BD and whether increased physical activity in high-risk individuals may act as a protective factor against development of psychiatric illness.

P0410SIGNIFICANT BURDEN OF DISEASE DURING MAINTENANCE TREATMENT OF ANCA-ASSOCIATED VASCULITIS (AAV) PATIENTS IN REAL WORLD PRACTICE IN EUROPE

Abstract Background and Aims ANCA associated vasculitis (AAV) is a relapsing remitting long term condition and patients are at risk of organ damage from both active AAV and its therapy in particular high dose and/or prolonged glucocorticoids (GC). The remission maintenance phase of AAV is critical for good long term outcomes including renal preservation as well as preventing AAV relapse. This retrospective study aimed to examine the definition of maintenance, therapy and clinical outcomes in patients managed in routine practice. Method 1478 AAV patients (France, Germany, Italy, Spain and UK) managed by 493 physicians (61% Nephrologists) who completed induction therapy for organ or life threatening AAV and initiated maintenance therapy between 2014-16 were studied. Data were collected retrospectively at the time maintenance was determined to begin by the physician and then at 6, 12, 18 and 36 months. Results 49% had granulomatosis with polyangiitis,; mean age 54.2 years with 56% male. 49% had incident AAV and 51% were studied from the time of a relapse requiring remission induction therapy. 70% received cyclophosphamide and GC and 30% received rituximab and GC as induction treatment with 28% receiving plasma exchange. Physicians defined time of the start of maintenance from induction treatment start with mean of 5.7 months on the basis of fixed time point 40%, starting new drug for maintenance 26%, reaching full remission 26% and no specific criteria 8%. At this time of maintenance start 43% were in full remission vs 50% in partial and 7% refractory. Various maintenance regimes were used, 21% received rituximab (88% 6 monthly and 8% 12 monthly, 4% other) at varying planned doses 34% 1g, 40% 500 mg and 23% 375 mg/m2, 4% other regime. Remission rates varied with patients experiencing disease relapse and many patients experienced adverse events (AE) and infections with prolonged GC use being common. Renal function was relatively unchanged and some patients had worsening eGFR, protein excretion or blood pressure. At the most recent clinical review patients had been followed for a mean of 50.7 months – 6% had died, 38% had relapsed at least once, and 11% required renal replacement therapy. 54% had no vasculitis activity, 26% were ANCA positive without active disease and 19% were still experiencing active disease. 32% were still receiving GCs - 22% of them receiving &amp;gt; 5mg/ day. Conclusion Maintenance therapy is variably defined but typically at 6 months from start of remission induction therapy. Achieving full remission and preventing relapse are still clinical problems and many patients require ongoing GC therapy to maintain remission. Infectious complications and adverse events are common and renal disease remains an ongoing clinical problem.

Real-life analysis of 280 patients with surgically treated acromegaly: a single-center experience from 2008 to 2015.

The purpose of this study was to analyze the clinical and biochemical outcome of consecutive patients with acromegaly after microscopic transsphenoidal surgery (MTS) at a single center over an 8-year period. A retrospective analysis of patients with acromegaly treated via MTS between 2008 and 2015 at the authors' center was performed. The mean follow-up was 29 months (range 1-120 months). Parameters investigated included tumor size, pre- and postoperative insulin-like growth factor-I, growth hormone levels, pretreatment, perioperative complications, and clinical outcome. A total of 280 patients with acromegaly were treated surgically at the authors' center over the abovementioned time frame and were included in analyses. For 231 of these patients, complete follow-up data were available for evaluation. One hundred eighty-eight patients (81%) showed remission initially according to current criteria. So far, 23 of these patients relapsed in the further course, so that on follow-up 165 patients (71%) demonstrated full remission by surgery alone. Most patients in whom remission after surgery failed were treated with somatostatin receptor ligands and/or dopamine agonists as second-line treatment. The main postoperative complications included transient hyponatremia and diabetes insipidus (13/280; 4.6%). CSF leakage only occurred in 2 cases (2/280; 0.7%). No surgery-related death occurred. The data underline the effectiveness of MTS in acromegaly. Many patients with recurrent disease or incomplete tumor resection can be successfully managed pharmacologically.

Vitrification of in vivo recovered equine embryos in France

It has been suggested that gluten may play a role in equine inflammatory small bowel disease (ISBD). Previous work showed an association between equine gluten-sensitive enteropathy and IgA antibodies to tissue transglutaminase (TGA) in serum. The purpose of this study is to investigate the prevalence of IgA antibodies to TGA in a group of healthy non–gluten-free sport ponies and to present a case of tentative gluten-sensitive enteropathy and dermatitis in a horse. Blood samples were obtained from 40 healthy jumping ponies. The ponies comprised 12 mares, 8 stallions, and 20 geldings with an average age of 9.0 ± 3.8 years (±SD; range 3–19 years). Sera were tested for IgA antibodies against human recombinant TGA. Significance (P < .05) of the correlation between TGA titer and age in these ponies was assessed using Pearson test (two tailed). In addition, to further illustrate tentative equine gluten-sensitive enteropathy and dermatitis, the clinical course in an 11-year-old Dutch Warmblood sport horse gelding has been described. The average TGA titer was 21.4 ± 13.6 AU/mL (range 2–65 AU/mL). There was a significant (P = .013) correlation (r = 0.389) between age and TGA titer in ponies. One of the 40 ponies (2.5%) showed an elevated TGA titer. An elevated TGA titer decreased after a gluten-free ration for 3 months in an 11-year-old Warmblood gelding with a tentative diagnosis of ISBD associated with full remission of the generalized skin reaction. To our best knowledge, this is the first study assessing TGA antibodies in sera from healthy non–gluten-free ponies and showing a correlation with age. The presented case could be the first one of a horse with a tentative diagnosis of gluten-sensitive enteropathy combined with dermatitis. Given the reported findings, this study warrants further investigations into gluten-sensitive enteropathy and dermatitis in individual horses affected with ISBD.

Precocious pseudopuberty, a paraneoplastic manifestation: a report of 2 cases

Peripheral precocious puberty (PPP) may be a paraneoplastic manifestation, associated with beta human chorionic gonadotropin (β-hCG)-secreting tumors. We describe 2 young children with β-hCG-secreting tumors presenting with signs of pubertal activation. In the first patient, a 16-month-old boy with hepatoblastoma, only initial signs of PPP at presentation were identifiable, with concomitant high levels of β-hCG. Although the tumor had good response to therapy, β-hCG levels were fluctuant until the tumor was resected surgically. The second patient, an 18-month-old boy with intracranial germ cell tumor, presented with clear signs of pubertal activation and genitalia enlargement with no initial alteration of sex hormones. In both cases, the oncologic response to therapy was good. In the first case, full remission of the pubertal signs was observed; in the second, pubertal signs were still visible 20 months after the end of treatment.

0919 Health Disparities in the Persistence of Childhood Insomnia Symptoms in the Transition to Adolescence: The Penn State Child Cohort

Abstract Introduction A strong body of cross-sectional evidence indicates that social determinants of health (SDH), such as race, ethnicity, socioeconomic status, and sex/gender, are linked to sleep problems, including insomnia symptoms. Few studies have examined the longitudinal association between SDH and the persistence and remission of insomnia symptoms in the transition between childhood and adolescence, a critical period for sleep health. Methods The Penn State Child Cohort is a random, population-based sample of 700 children (5-12y at baseline), of whom 421 were followed up as adolescents (12-23y at follow-up). All subjects underwent polysomnography, clinical history, physical exam, and parent- and self-reported scales at baseline and follow-up. Childhood insomnia symptoms were defined as a parent- and/or self-report of difficulty falling and/or staying asleep. All subjects or their parents identified the subject’s sex, race, and ethnicity, and reported on socioeconomic status (SES) of the household. Results Females (32.7%) and racial/ethnic minorities (25.0%) were associated with a significantly lower remission rate as compared to males (53.3%) and non-Hispanic whites (48.3%), respectively. Non-Hispanic whites of low SES were associated with a significantly lower full remission rate (26.3%) as compared to non-Hispanic whites of higher SES (42.0%), while racial/ethnic minorities were associated with the lowest full remission rates regardless of whether they were of low (9.1%) or higher (11.1%) SES. Conclusion Our novel data indicate that gender-, racial/ethnic- and socioeconomic-related disparities in insomnia not only occur as early as childhood but are important determinants of insomnia’s chronic course throughout development. Support National Institutes of Health (R01HL136587, R01HL97165, R01HL63772, UL1TR000127)

Fatigue nach Kopf-Hals-Tumorleiden – Ergebnisse einer Befragung mit dem Multidimensional Fatigue Inventory (MFI-20)

Fatigue resulting from cancer and its treatment can lead to areduction in quality of life. The frequency and intensity of fatigue syndrome after cancer therapy in the ENT field are largely unknown. Therefore, during follow-up consultations, the authors conducted arandom survey with the help of the Multidimensional Fatigue Inventory (MFI20). During aftercare consultations, 66patients were interviewed (average age 63years, 21women). All patients had received radiotherapy an average of 2years previously (range 1-4years). All respondents were in full remission at the time of the survey. According to recommendations, evaluation of the MFI-20 was carried out in 5subgroups: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. For comparison with standard values, respondents were grouped by age into under and over 60 years and were also evaluated by gender. Regardless of gender, our patients reported clearly elevated scores in all subgroups. Particularly participants aged under 60years reported very high scores. The clarity of the results surprised the authors. Fatigue represents avery profound and prolonged impairment for the patients of our study. Since fatigue can still be present a long time after completion of treatment, patients should be asked about it specifically using a standardized inventory during follow-up. In order to cope with fatigue syndrome, specific therapeutic recommendations aimed at activation, such as regular physical activity, nutritional advice, and complementary measures, can be made.

Neuroscience of Adolescent Anorexia Nervosa: Implications for Family-Based Treatment (FBT).

Over the past 20 years significant progress has been made to elucidate some of the neurobiological underpinnings of the development and maintenance of anorexia nervosa and their possible implications for treatment. There is increasing evidence supporting the notion that anorexia nervosa shares neurobehavioral patterns with anxiety disorders and involves reward processing aberrations and habit formation. There is consensus for the need of early intervention to ameliorate the effects of starvation on the adolescent brain and the effects of illness duration on neurodevelopment. Family-based treatment (FBT) is the first line evidence-based treatment for adolescents with anorexia nervosa achieving sustainable full remission rates of over 40%. FBT has an agnostic treatment approach and its mechanisms of change have until now not been fully understood. To help fill this gap in theoretical understanding, this paper will provide a review of the treatment model of FBT through a neuroscientific lens. It argues that FBT is well designed to address the implications of current key findings of the neuroscience of anorexia nervosa and that it is also well aligned with the current understanding of neuroscience principles underpinning therapeutic change. The paper supports the perspective that FBT utilizes principles of parent facilitated exposure response prevention. It concludes that an integration of a neuroscience perspective to the provision of FBT will assist the clinician in their practice of FBT.

A Monocentric, Retrospective Analysis of 61 Patients with Generalized Granuloma Annulare

Background: Granuloma annulare is a chronic noninfectious granulomatous skin condition with variable clinical presentations. Generalized granuloma annulare, defined as widespread disease with >10 skin lesions, accounts for 15% of all cases. Numerous associated diseases have been controversially discussed, most importantly diabetes mellitus, dyslipidemia, thyroid disease, malignancy and systemic infections. Objectives: The objective of our study is to describe disease characteristics, treatment outcome and associated diseases in patients treated at the Department of Dermatology of the University Hospital Zurich during the last 20 years. Methods: The hospital database was searched for patients with generalized granuloma annulare in the last 20 years (January 1, 1998, to December 31, 2017). Overall, 61 patients, 14 males and 47 females, were included in our study. The mean age was 58 years at first consultation. The diagnosis was verified clinically and histologically. Results: Generalized granuloma annulare occurred at a mean age of 55 years, more commonly in females. Pruritus was absent in 51% of all patients. Metabolic diseases including diabetes mellitus, hypercholesterinemia and hypertriglyceridemia were present in 10.5, 8.2 and 4.9%, respectively. Thyroid disease was present in 9.8% and malignant disease in 23%, including colorectal cancer, lymphoproliferative disease, squamous cell carcinoma of the esophagus, basal cell carcinoma and gynecological malignancy. Therapy was initiated in 92%, while second- and third-line therapy was performed in 70 and 39%, respectively. Benefit during therapy (e.g., full and partial remission) was achieved in 39.3% during first-line, in 39.4% during second-line and in 33.8% during third-line treatment. Topical corticosteroids were the most commonly prescribed treatment, mostly leading to stable disease (46.6%). Combined full and partial remission occurred in a large proportion of patients receiving UVA1 (45%), PUVA (63.6%) and intralesional triamcinolone acetonide (100%). Conclusions: Generalized granuloma annulare is a mostly asymptomatic and benign disease with a strong tendency for treatment resistance. We suggest to screen all patients for dyslipidemia, thyroid disease and malignant disease. While randomized trials are needed, we suggest topical corticosteroids as the first-line treatment, intralesional triamcinolone acetonide for persistent solitary lesions and, if further treatment is needed, UVA1 or PUVA.

Potential Therapeutic Role of Carnitine and Acetylcarnitine in Neurological Disorders.

Current therapy of neurological disorders has several limitations. Although a high number of drugs are clinically available, several subjects do not achieve full symptomatic remission. In recent years, there has been an increasing interest in the therapeutic potential of L-carnitine (LCAR) and acetyl-L-carnitine (ALCAR) because of the multiplicity of actions they exert in energy metabolism, as antioxidants, neuromodulators and neuroprotectors. They also show excellent safety and tolerability profile. To assess the role of LCAR and ALCAR in neurological disorders. A meticulous review of the literature was conducted in order to establish the linkage between LCAR and ALCAR and neurological diseases. LCAR and ALCAR mechanisms and effects were studied for Alzheimer's disease, depression, neuropathic pain, bipolar disorder, Parkinson's disease and epilepsy in the elderly. Both substances exert their actions mainly on primary metabolism, enhancing energy production, through β-oxidation, and the ammonia elimination via urea cycle promotion. These systemic actions impact positively on the Central Nervous System state, as Ammonia and energy depletion seem to underlie most of the neurotoxic events, such as inflammation, oxidative stress, membrane degeneration, and neurotransmitters disbalances, present in neurological disorders, mainly in the elderly. The impact on bipolar disorder is controversial. LCAR absorption seems to be impaired in the elderly due to the decrease of active transportation; therefore, ALCAR seems to be the more effective option to administer. ALCAR emerges as a simple, economical and safe adjuvant option in order to impair the progression of most neurological disorders.

Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression

Treatment-resistant depression (TRD) is a serious problem in adolescents. Development and optimization of novel interventions for these youth will require a deeper knowledge of the neurobiology of depression. A well-established phenomenon of depression is an attention bias toward negativity and away from positivity that is evidenced behaviorally and neurally, but it is unclear how symptom reduction is related to changes to this bias. Neurobiological research using a treatment probe has promise to help discover the neural changes that accompany symptom improvement. Ketamine has utility for such research because of its known rapid and strong antidepressant effects in the context of TRD. Our previous study of six open-label ketamine infusions in 11 adolescents with TRD showed variable response, ranging from full remission, partial response, non-response, or clinical worsening. In this study, we examined the performance of these participants on Word Face Stroop (WFS) fMRI task where they indicated the valence of affective words superimposed onto either congruent or incongruent emotional faces before and after the ketamine infusions. Participants also completed a clinical assessment (including measurement of depression symptomology and anhedonia/pleasure) before and after the ketamine infusions. Following ketamine treatment, better WFS performance correlated with self-reported decreased depressive symptoms and increased pleasure. Analyses of corticolimbic, corticostriatal and default mode (DMN) networks showed that across networks, decreased activation during all conditions (congruent negative, congruent positive, incongruent negative, and incongruent positive) correlated with decreases in depressive symptoms and with increases in pleasure. These findings suggest that in adolescents with TRD, clinical improvement may require an attenuation of the negativity bias and re-tuning of these three critical neural networks to attenuate DMN and limbic regions activation and allow more efficient recruitment of the reward network. Lower activation across conditions may facilitate shifting across different salient emotional stimuli rather than getting trapped in downward negative spirals.

Potential depression and antidepressant-response biomarkers in human lymphoblast cell lines from treatment-responsive and treatment-resistant subjects: roles of SSRIs and omega-3 polyunsaturated fatty acids.

While several therapeutic strategies exist for depression, most antidepressant drugs require several weeks before reaching full biochemical efficacy and remission is not entirely achieved in many patients. Therefore, biomarkers for depression and drug-response would help tailor treatment strategies. This study made use of banked human lymphoblast cell lines (LCLs) from normal and depressed subjects; the latter divided into remitters and non-remitters. Due to the fact that previous studies have shown effects on growth factors, cytokines and elements of the cAMP generating system as potential biomarkers for depression and antidepressant action, these were examined in LCLs. Initial gene and protein expression profiles for signaling cascades related to neuroendocrine and inflammatory functions differ among the three groups. Growth factor genes, including VEGFA and BDNF were significantly down-regulated in cells from depressed subjects. In addition, omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to act as both antidepressants and anti-inflammatories, but the mechanisms for these effects are not established. Here we showed that n-3 PUFAs and escitalopram (selective serotonin reuptake inhibitors, SSRIs) treatment increased adenylyl cyclase (AC) and BDNF gene expression in LCLs. These data are consistent with clinical observations showing that n-3 PUFA and SSRI have antidepressant affects, which may be additive. Contrary to observations made in neuronal and glial cells, n-3 PUFA treatment attenuated cAMP accumulation in LCLs. However, while lymphoblasts show paradoxical responses to neurons and glia, patient-derived lymphoblasts appear to carry potential depression biomarkers making them an important tool for studying precision medicine in depressive patients. Furthermore, these data validate usefulness of n-3 PUFAs in treatment for depression.

Naturalistic follow-up in bipolar patients after successful electroconvulsive therapy

BackgroundElectroconvulsive therapy (ECT) is an effective treatment for acute depression, mania and mixed states. We evaluated the long-term outcome of patients with bipolar depression or mixed state, responsive to ECT. Methodsthis observational follow-up study was conducted in 70 patients with Bipolar Disorder: 36 patients met DSM-IV-TR criteria for a major depressive episode (MDE) and 34 for a mixed episode (MXE). During the follow-up after ECT, the relapse rates and the duration of response and remission periods were recorded. Resultsthe mean duration of the follow-up was 57 weeks. 93% of the patients maintained at least a partial therapeutic response for more than 90% of the follow-up period. 73% of patients fulfilled the criteria for a full remission, 33% showed a depressive relapse and 10% a mixed relapse. No manic relapses occurred but almost 1/3 of the sample presented hypomanic episodes. MDE patients presented higher rates of remission compared to MXE ones. Patients with anxiety disorders reported earlier relapses than those without this comorbidity. Relapsed-patients showed higher functional impairment at baseline evaluation, compared to non-relapsed ones. Limitationsnonrandom allocation, limited sample size, possible influence of psychopharmacological treatment. ConclusionsGiven several methodological limitations, this study cannot draw definite conclusions but could suggest that in treatment-resistant bipolar patients with severe depression or mixed state, ECT may represent a useful treatment option. Patients with mixed features, comorbid anxiety disorders and higher functional impairment present less favorable outcome. Future research on long-term efficacy of ECT and on clinical predictors of relapse is needed.

Khat induced psychotic disorder: case report

BackgroundKhat (Catha edulis) is a stimulant leaf khat comes from a tree which grows in countries bordering the Red Sea which are along the east coast of Africa and in west Asia. The psycho- active component within these leaves is cathinone. In Ethiopia, Khat is chewed routinely by users for its euphoric effects and as a recreational drug, and chewing khat has an important role as well in both traditional and religious ceremonies. In this case report, we describe the case of a 33-year-old male patient presented with psychotic symptoms after prolonged and heavy khat chewing.Case presentationFindings on psychiatric evaluation encompassing detailed history and mental state examination suggest khat induced psychotic disorder severe in full remission; khat use disorder, severe, in early remission.ConclusionsThis case demonstrates that the use of excess khat above 2 bundles for prolonged duration can manifest with psychotic episodes. A small number of case studies had supported a causal relationship between heavy khat use and psychosis or psychotic symptoms. There have been suicidal attempts and homicidal acts in those who used excess and prolonged use of khat. In our case, the improvement attributed to stopping the khat rather than taking antipsychotics.Therefore, we recommend an urgent social intervention to change the community norms regarding Khat use through psycho-education in media, institution and in person about the relationship between khat use and mental illness. In addition, we suggest the role of religious institutions on the management of khat use not be overlooked. Finally, this study makes a powerful argument for researchers and policy makers to do clinical study to settle a causal effect relation of khat on mental health.