Treatment Of Affective Disorders Research Articles

Lysophosphatidic acid induces thrombospondin-1 production in primary cultured rat cortical astrocytes.

Lysophosphatidic acid (LPA), a brain membrane-derived lipid mediator, plays important roles including neural development, function, and behavior. In the present study, the effects of LPA on astrocyte-derived synaptogenesis factor thrombospondins (TSPs) production were examined by real-time PCR and western blotting, and the mechanism underlying this event was examined by pharmacological approaches in primary cultured rat cortical astrocytes. Treatment of astrocytes with LPA increased TSP-1 mRNA, and TSP-2 mRNA, but not TSP-4 mRNA expression. TSP-1 protein expression and release were also increased by LPA. LPA-induced TSP-1 production were inhibited by AM966 a LPA1 receptor antagonist, and Ki16425, LPA1/3 receptors antagonist, but not by H2L5146303, LPA2 receptor antagonist. Pertussis toxin, Gi/o inhibitor, but not YM-254890, Gq inhibitor, and NF499, Gs inhibitor, inhibited LPA-induced TSP-1 production, indicating that LPA increases TSP-1 production through Gi/o-coupled LPA1 and LPA3 receptors. LPA treatment increased phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK). LPA-induced TSP-1 mRNA expression was inhibited by U0126, MAPK/ERK kinase (MEK) inhibitor, but not SB202190, p38 MAPK inhibitor, or SP600125, JNK inhibitor. However, LPA-induced TSP-1 protein expression was diminished with inhibition of all three MAPKs, indicating that these signaling molecules are involved in TSP-1 protein production. Treatment with antidepressants, which bind to astrocytic LPA1 receptors, increased TSP-1 mRNA and protein production. The current findings show that LPA/LPA1/3 receptors signaling increases TSP-1 production in astrocytes, which could be important in the pathogenesis of affective disorders and could potentially be a target for the treatment of affective disorders.

Reframing the Past: Role of Memory Processes in Emotion Regulation

The ability to modulate undesirable emotions is essential for maintaining mental health. Negative emotions can arise both while experiencing and remembering an unpleasant event, which presents a persistent emotion regulation challenge because emotional memories tend to be particularly vivid and enduring. Despite the central role that memories play in our affective lives, little is known about the memory processes supporting successful regulation of emotions associated with long-term memories, which we refer to as retrospective emotion regulation. In this paper, we review the literature on the mechanisms of memory modification, which may contribute to the success of retrospective emotion regulation. In particular, we review rodent and human studies that examine the modification of conditioned fear associations and emotional episodic memories. Based on this literature, we conclude that memory reactivation plays a crucial role in memory modification. We discuss further the potential role of memory reactivation in mediating the success of cognitive reappraisal, which may be considered a special case of memory modification. We propose that the completeness, or strength, of reactivation during retrospective emotion regulation will be related to the likelihood of updating an episodic memory, reducing its emotional impact upon later recall. Understanding the role of memory processes in emotion regulation can help to inform research on memory-based treatments for affective disorders.

A half-century of participant observation in psychiatry. Part II: Affective disorders.

The last half-century, thanks to the efforts of outstanding researchers, brought about great progress in the pathogenesis and clinics of affective illnesses. The catecholamine and serotonin hypothesis delineated in the 1960s have retained significant merit. Since the 1990s, the theories have pointed on excessive immune activation and impairment of neuroplasticity under stress. Since the 1970s, asystematic subclassification of unipolar and bipolar affective disorder has proceeded. Epidemiological studies of the last half-century indicated a significantly higher prevalence of depression compared with previous decades. The 21st century brought evidence for agreater frequency of various forms of bipolar affective disorder. During the last 50years, the etiopathogenesis, diagnosis and treatment of affective disorders were my favorite and fascinating clinical and research topics. This initiated in 1970 when I began my work in the Department of Psychiatry, Medical Academy in Poznan, on account of the introduction of lithium salts for the treatment of these disorders. In 1976-1977, I received afellowship of the National Institutes of Health at the University of Pennsylvania in Philadelphia and participated in research that elucidated the mechanism of lithium transport across cell membranes. I carried out the studies on the pathogenesis of affective disorders for more than 40 years afterward. They concerned abnormalitiesof transport across cell membranes, the activity of stress system, excessive pro-inflammatory activation, molecular genetics, dysfunctions of cognition and neurotrophins, especially the brain-derived neurotrophic factor (BDNF). Atthe beginning of the 21st century, I coordinated two Polish epidemiological projects DEP-BI and TRES-DEP. For my research on bipolar disorders, I received many international awards. I am also the author of the book The faces of manic-depressive illness which had three Polish editions as well as English and Russian versions.

Cyclooxygenase-2 inhibition prevents stress induced amygdala activation and anxiety-like behavior

Stress is a major risk factor for the development and exacerbation of mood and anxiety disorders, and recent studies have suggested inflammatory contributions to the pathogenesis of depression. Interestingly, pharmacological inhibition of cyclooxygenase-2 (COX-2) has shown promise in the treatment of affective disorders in small scale clinical studies; however, the mechanisms by which COX-2 inhibition affects behavioral domains relevant to affective disorders are not well understood. Here, we examined the effects of pharmacological inhibition of COX-2 with the highly selective inhibitor Lumiracoxib (LMX) on anxiety-like behavior and in vivo basolateral amygdala (BLA) neural activity in response to acute restraint stress exposure. In male mice, pretreatment with LMX prevented the increase in BLA calcium transients induced by restraint stress and prevented anxiogenic behavior seen after restraint stress exposure. Specifically, acute injection of LMX 5 mg kg−1 reduced anxiety-like behavior in the light–dark box (LD) and elevated-zero maze (EZM). In addition, in vivo fiber photometry studies showed that acute stress increased calcium transients and the predicted action potential frequency of BLA neurons, which was also normalized by acute LMX pretreatment. These findings indicate pharmacological inhibition of COX-2 can prevent acute stress-induced increase in BLA cellular activity and anxiety-like behavior and provides insights into the neural mechanisms by which COX-2 inhibition could affect anxiety domain symptoms in patients with affective disorders.

Affective disorders: A question of continuing treatment during pregnancy (Review).

Fetal development, especially in the first trimester, has proven to be heavily influenced by external factors, such as chemical intake of medication. Chronic psychiatric treatment might interfere with the anatomical and physiological wellbeing of the fetus, because psychotropic medication proceeds past the placenta, into the amniotic fluid, and can enter breast milk. Hence some of the medications prescribed for mood disorders should be reconsidered during pregnancy, without sub-optimally treating when it is needed. A literature review is presented which systematically collects modern data and synthesizes previous interdisciplinary research findings on the safety of psychiatric treatment for affective disorders during pregnancy (term-based) and lactation. Antidepressants and mood stabilizers, fundamental strategies in treating affective disorders, have been classified by the FDA as C respectively D drugs pertaining to their risk, with some exception. Most guidelines recommend pharmacologically treating moderate-severe depression, preferably with SSRIs. Evidence advocates that drugs should be used during pregnancy only if clearly needed and the benefit outweighs the risk to the fetus. However, guidelines the American College of Obstetricians and Gynecologists state that antidepressants are a preferred first course of treatment and does not take into account the severity of the depression. Among mood-stabilizers, lithium is considered to be the safest option for pregnant women. Anticonvulsants have a higher risk of teratogenicity compared with lithium, with lamotrigine being the safest one. All mood stabilizers should be recommended in the lowest effective doses. There is controversy regarding the safety of second-generation antipsychotics during pregnancy and further research is required. Several case reports and meta-reviews have been published in order to emphasize the safety of electroconvulsive therapy (ECT) during pregnancy, but practitioners still stigmatize this procedure. Evaluating the overall risk-benefit ratio should be assessed by the medical care provider, taking into consideration current findings.

Annual Prevalence of Use of Potentially Inappropriate Medications for Treatment of Affective Disorders in Parkinson's Disease

To examine the national prevalence of pharmacological treatment of affective disorders in older adults with Parkinson's disease (PD), and determine the prevalence and risk factors for receipt of an American Geriatrics Society Beers Criteria® defined potentially inappropriate medication (PIM) for affective disorder treatment. Cross-sectional analysis of 2014 Medicare data. Research Identifiable File data from the Centers for Medicare and Medicaid Services. Individuals ≥65 years of age with PD whose inpatient, outpatient, and prescription care is administered through the U.S. Medicare Program. The 2014 prevalence of affective (i.e., depressive and anxiety) disorders was calculated. We assessed prescription fills for affective disorder treatment and classified prescriptions according to PIM status. Patient and clinician factors associated with PIM prescriptions were determined. Of 84,323 beneficiaries with PD, 15.1% had prevalent depression only, 7.5% had anxiety only, and 8.5% had comorbid depression and anxiety. Among those with depression only, 80.7% were treated in 2014 (12.8% of treated received at least one PIM). The annual treatment prevalence was 62.9% (75.9% PIM) and 93.1% (63.9% PIM) in the anxiety only and comorbid group, respectively. In most groups, PIM use was less likely among men and those with dementia; geriatricians were less likely to prescribe PIMs. Treatment of affective disorders in persons diagnosed with PD is high. PIM use is also common, particularly in persons with anxiety. Future research will quantify the potential effects of these PIMs on clinical and patient outcomes.

Cognitive Vulnerabilities as Prognostic Predictors of Acute and Follow-up Outcomes in Seasonal Affective Disorder Treatment with Light Therapy or Cognitive-Behavioral Therapy.

First-line treatments for winter seasonal affective disorder include light therapy and cognitive-behavioral therapy; however, it is unclear whether particular patient profiles respond differentially to each treatment type. This study examined baseline patient cognitive and chronobiological vulnerabilities as prognostic and prescriptive predictors of acute and follow-up treatment outcomes. 177 adults with seasonal affective disorder were randomized to 6-weeks of either light therapy or cognitive-behavioral therapy. Participants completed baseline measures of cognitive vulnerabilities (Dysfunctional Attitudes Scale; Ruminative Response Scale; Seasonal Belief Questionnaire) and chronobiological vulnerability (Morningness-Eveningness Questionnaire). Depression was assessed at pre- and post-treatment and at follow-ups one and two winters later. Pre-treatment depression severity correlated significantly with each cognitive vulnerability measure, and significantly predicted future depression. After controlling for pre-treatment depression, higher scores on the Morningness-Eveningness Questionnaire were prognostic of lower depression at treatment endpoint, but no cognitive vulnerability emerged as a prognostic or prescriptive predictor of outcome. Greater morningness was associated with less severe post-treatment depression in both cognitive-behavior therapy and light therapy. No cognitive vulnerability emerged as a prognostic or prescriptive predictor, perhaps because they correlated with pre-treatment depression severity, a robust predictor of outcome. Future research should test alternative cognitive constructs.

The role of eugeroics in the treatment of affective disorders.

Eugeroics are a relatively new class of wakefulness-promoting agents. Thegroup includes adrafinil, modafinil and armodafinil. Modafinil is the most widely used and the best studied agent. Indications for the use of modafinil include the treatment of narcolepsy, shift-work sleep disorders and excessive daytime sleepiness associated with obstructive sleep apnea. Many studies show the utility of modafinil and armodafinil in the treatment of depression - both in monotherapy andas potentiation therapy if needed. Modafinil has proven to be effective in the treatment of residual symptoms of unipolar and bipolar depression such as fatigue, excessive sleepiness and some cognitive impairment. Research on armodafinil points to its effectiveness mainly in augmentation therapy of depression in the course of bipolar disorder. There are also reports on the effectiveness of eugeroics in special cases - seasonal depression, atypical depression with hyperphagia, apathy in the course of depression or as an isolated symptom, cancer-related fatigue in patients receiving chemotherapy, fatigue and excessive sleepiness in neurological diseases. Eugeroics due to their high selectivity of action in the CNS have a low addictive potential compared with other stimulants. The risk of manic switch is comparable to placebo. In general, they are well-tolerated and safe. The purpose of this paper is to review the literature on the use of eugeroics in the treatment of affective disorders.

Epidemiology and outcome of idiopathic generalized epilepsy in adults.

Drug-resistant idiopathic generalized epilepsy (IGE) remains challenging despite a favourable overall prognosis of IGE, and little is known about basic epidemiology and long-term outcome of drug-resistant IGE. The aim of the study was to describe the incidence, prevalence and outcome of IGE in an unbiased, population-based cohort. In 2014-2018, all patients (≥17years) with IGE inhabiting the island of Funen (496000 inhabitants) were recruited. The socioeconomic and clinical information available for 406 individuals was assessed. Median follow-up was 15years. The average IGE incidence (2008-2017) was 2.9/100000 inhabitants/year. The point prevalence of identifiable IGE patients was 1.0/1000 adults (juvenile myoclonic epilepsy 0.4/1000; absence epilepsy 0.3/1000, epilepsy with generalized tonic-clonic seizures alone 0.3/1000); 92.1% of the patients were diagnosed before 25years of age. When correcting for unequal age distribution in the cohort, 1102 people on the island of Funen fulfilled the diagnostic criteria for IGE at the age of 25 (estimated prevalence 2.7/1000 adults). In the year before data closure, 121 patients reported seizures. Fifty patients met the definition of drug-resistant IGE (12.1% of the cohort, 4.5% of the estimated 1102 IGE patients). The average seizure burden of all patients with drug-resistant IGE was 2.2 generalized tonic-clonic seizures per year; only 14 patients suffered more than two generalized tonic-clonic seizures per year. Drug-resistant IGE was associated with an increased risk of requiring treatment for affective disorders and a reduced probability of working full time. Idiopathic generalized epilepsy was associated with a low risk of persistent drug-resistant seizures requiring specialist medical attention. Drug resistance was associated with a negative socioeconomic outcome.

Lithium in the psychopharmacology of affective disorders and mechanisms of its effects on cellular physiology

However, despite successful use of lithium in the treatment of affective disorders for almost 40 years, the mechanisms of its therapeutic action are still poorly understood. This review presents and summarizes the current literature about the use of lithium in treatment of affective disorders, as well as its effects on cellular physiology, with a separate description of the effect of this ion on the functioning of nerve tissue and ion-molecular mechanisms.

The therapeutic potential of microdosing psychedelics in depression.

Microdosing psychedelics is the repeated use of small doses of, for example, lysergic acid diethylamide (LSD) and psilocybin, typically for a few weeks. Despite the popular and scientific attention in recent years, and claims by users that it has therapeutic value in affective disorders like depression, little scientific knowledge is available to back this. The purpose of this review was to investigate whether there are scientific grounds to state that this practice could be helpful in the treatment of affective disorders, and safe to use repeatedly. To that end, the literature (PubMed, MedLine) was searched, looking for (controlled) experimental studies with low doses of LSD and/or psilocybin, in healthy volunteers and patient samples. After a selection process and the addition of relevant articles, 14 experimental studies entered this review. Findings show that both LSD (10–20 mcg) and psilocybin (<1–3 mg) have subtle (positive) effects on cognitive processes (time perception, convergent and divergent thinking) and brain regions involved in affective processes. Besides the pleasant experience, increased anxiety and a cycling pattern of depressive and euphoric mood were also found. With regard to safety, it was demonstrated that low doses are well tolerated (in healthy volunteers) and have no-to-minimal effects on physiological measures. While it is yet unclear whether psychedelic microdosing is of therapeutic value for depression, the aforementioned effects on selective processes suggest that low doses of psychedelics could play a role in depression by inducing some kind of cognitive flexibility, which might lead to decreased rumination. While previous studies were conducted mostly in small samples of healthy volunteers, future placebo-controlled clinical trials in depressed patients are required to understand the therapeutic value of microdosing psychedelics, how this differs from therapy using full psychedelic doses, and whether different psychedelics have different effect patterns. The proposed research will give new insights into the potential of future alternative psychiatric treatment forms that are fiercely needed.

Brain GABA+ changes in primary hypothyroidism patients before and after levothyroxine treatment: A longitudinal magnetic resonance spectroscopy study

ObjectiveIncreasing evidence indicates the involvement of the GABAergic system in the pathophysiology of hypothyroidism. We aimed to investigate longitudinal changes of brain GABA in primary hypothyroidism before and after levothyroxine (L-T4) treatment. Material and methodsIn 18 patients with hypothyroidism, we used the MEGA-PRESS (Mescher-Garwood point-resolved spectroscopy) editing sequence to measure brain GABA levels from medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) at baseline and after 6-months of L-T4 treatment. Sex- and age-matched healthy controls (n = 18) were scanned at baseline. Thyroid function and neuropsychological tests were also performed. ResultsGABA signals were successfully quantified from all participants with fitting errors lower than 15%. GABA signal was labeled as GABA+ due to contamination from co-edited macromoleculars and homocarnosine. In hypothyroid patients, mean GABA+ was significantly lower in the mPFC region compared with controls (p = 0.031), and the mPFC GABA+ measurements were significantly correlated with depressive symptoms and memory function (r = −0.558, p = 0.016; r = 0.522, p = 0.026, respectively). After adequate L-T4 treatment, the mPFC GABA+ in hypothyroid patients increased to normal level, along with relieved neuropsychological impairments. ConclusionThe study suggested the decrease of GABA+ may be an important neurobiological factor in the pathophysiology of hypothyroidism. Treatment of L-T4 may reverse the abnormal GABA+ and hypothyroidism-induced neuropsychiatric impairments, indicating the action mode of L-T4 in adjunctive treatment of affective disorders.

Use of long acting antipsychotics and relationship to newly diagnosed bipolar disorder: a pragmatic longitudinal study based on a Canadian health registry.

Background:There is limited data from large naturalistic studies to inform prescribing of long-acting injectable medication (LAIs). Guidance is particularly rare in the case of primary mood disorders.Methods:This study describes prescribing trends of LAIs in 3879 patients in Quebec, Canada, over a period of 4 years. Health register data from the Quebec provincial health plan were reviewed.Results:In this specific registry, 32% of patients who received LAIs drugs for schizophrenia had a confirmed diagnosis of bipolar disorder and 17% had a diagnosis of major depressive disorder. Non-schizophrenia syndromes were preferentially prescribed risperidone long-acting antipsychotic, whereas patients with schizophrenia were prescribed an excess of haloperidol decanoate. Patients with non-schizophrenia disorders prescribed long-acting antipsychotics were more frequently treated in primary care compared with patients with schizophrenia.Conclusion:Data from a large number of patients treated naturalistically in Quebec with long-acting antipsychotics suggests that these compounds, prescribed to treat symptoms of schizophrenia and schizoaffective disorders, were maintained when mood symptoms emerged, even in cases when the diagnosis changed to bipolar disorder. This pragmatic study supports the need to explore this intervention as potential treatment for affective disorders.

Thyroid hormone levels and ultrasonographic changes in thyroid gland of patients on long-term lithium treatment for affective disorders: A controlled study

Background: Although lithium is known to cause thyroid dysfunction and increased thyroid gland volume, clinical examination and biochemical assessment are fundamental to thyroid workup of patients on lithium treatment. We aimed to determine the thyroid gland volume and the thyroid hormone levels of patients who have been receiving lithium treatment for affective disorders in comparison to voluntary healthy controls. Materials and Methods: This was a cross-sectional, hospital-based observational study, performed in 43 patients on long-term lithium treatment for bipolar disorder, major depressive disorder, and schizoaffective disorder. Patients with documented continuous and adequate serum lithium levels for more than or equal to 6 months recruited consecutively underwent ultrasonographic examination of the thyroid gland. Ultrasonographic examinations were also done in all gender- and age-matched healthy controls. All cases and controls underwent biochemical thyroid function tests. Results: There were no statistically significant differences in gender (P = 0.198; χ2 = 1.654) of cases and controls. Most of the cases were married; maximum number of them unemployed and belonged to the lower socioeconomic status. Total thyroid volume was significantly greater in the lithium-treated group than the control group (9.40 ± 1.41 vs. 4.79 ± 0.45). Clinical inspection and palpation only detected goiter in six (n = 6, 13.95%) of patients on lithium and none among controls. The mean triiodothyronine (T3), mean thyroxine (T4), and mean scores for thyroid-stimulating hormone were significantly increased in patients receiving lithium therapy as compared to controls. Conclusion: It would seem wise from a clinical point of view to include ultrasonographic examination of the thyroid gland as part of the standard thyroid workup before initiating lithium treatment.

Thyroid hormone levels and Thyroid Hormone Levels and Ultrasonographic Changes in the Thyroid Gland of Patients on Long-Term Lithium Treatment for Affective Disorders: A Controlled Study.

Background:Although lithium is known to cause thyroid dysfunction and increased thyroid gland volume, clinical examination and biochemical assessment are fundamental to thyroid workup of patients on lithium treatment. We aimed to determine thyroid gland volume and the Thyroid hormone levels of patients who have been receiving lithium treatment for affective disorders in comparison to voluntary healthy controls.Methods:This was a cross-sectional, hospital-based observational study which was performed in 43 patients on long-term lithium treatment for bipolar disorder, major depressive and schizoaffective disorders. Patients with documented continuous and adequate serum lithium levels for more than or equal to 6 months recruited consecutively underwent the ultrasonographic examination of the thyroid gland. Ultrasonographic examinations were also done in all gender- and age-matched healthy controls. All cases and controls underwent biochemical thyroid function tests.Results:There were no statistically significant differences in gender (P = 0.198; Chi-square = 1.654) of cases and controls. Most of the cases were married, maximum number of them unemployed and belonged to the lower socioeconomic status. Total thyroid volume was significantly greater in the lithium-treated group than the controls (9.40 ± 1.41 vs. 4.79 ± 0.45). Clinical inspection and palpation only detected goiter in six (n = 6, 13.95%) of patients on lithium and none among controls. The mean triiodothyronine, mean thyroxine, and mean scores for thyroid-stimulating hormone were significantly increased in patients receiving lithium therapy as compared to controls.Conclusion:It would seem wise from a clinical point of view to include ultrasonographic examination of the thyroid gland as part of the standard thyroid workup before initiating lithium treatment.

Subcutaneous Mycobacterium vaccae promotes resilience in a mouse model of chronic psychosocial stress when administered prior to or during psychosocial stress

Chronic psychosocial stress is a risk factor for many mental disorders, including affective disorders, anxiety disorders, and trauma- and stressor-related disorders (i.e., posttraumatic stress disorder, PTSD). As these disorders are associated with an overreactive immune system and chronic low-grade inflammation, immunoregulatory approaches counterbalancing basal and/or stress-induced immune activation should be protective in this context. In support of this hypothesis, we recently demonstrated that repeated subcutaneous (s.c.) preimmunization with a heat-killed preparation of the immunoregulatory bacterium Mycobacterium vaccae (M. vaccae; National Collection of Type Culture (NCTC) 11659) promoted proactive stress coping and protected against stress-induced anxiety and intestinal pathology in a mouse model of chronic psychosocial stress. To induce development of a chronic anxiety-like state, the chronic subordinate colony housing (CSC) paradigm was used. Here we employed the CSC paradigm (start day 1) to confirm the stress-protective effects of repeated s.c. M. vaccae administrations prior to CSC exposure (days −21, −14, and −7) and to extend these findings to the stress-protective role of M. vaccae when administered repeatedly during CSC exposure (days 2, 8 and 15). As readouts we assessed the stress coping behavior on days 1, 8, and 15 and general and/or social anxiety-related behavior on days 19 (elevated plus-maze), 20 (open-field/novel object test), and day 21 (social preference/avoidance test) of CSC exposure. In line with our previous study, M. vaccae administered prior to CSC strongly promoted active stress coping and moderately reduced CSC-induced general and social anxiety. Although M. vaccae administered during CSC did not affect stress coping, this treatment protocol profoundly protected against CSC-induced general, and to a lesser extent social, anxiety. Taken together, these data broaden the framework for developing bioimmunoregulatory approaches, based on the administration of immunoregulatory microorganisms, for the prevention and/or treatment of affective disorders, anxiety disorders, and trauma- and stressor-related psychiatric disorders like PTSD.

Putative novel neuromodulatory treatments for affective disorders – What might emerge?

Putative novel neuromodulatory treatments for affective disorders – What might emerge?

Ancestral Fluoxetine Exposure Sensitizes Zebrafish to Venlafaxine-Induced Reductions in Cortisol and Spawning.

Owing to the prevalence of depression during childbearing, mothers can be prescribed multiple antidepressants; however, little is known about the risk and consequences to the offspring or subsequent generations. Fluoxetine (FLX) is usually the first-line of pharmacological treatment for affective disorders in pregnant women, with venlafaxine (VEN) used as secondary treatment. Given that FLX and VEN readily cross the placenta, a fetus from a treated pregnant woman is potentially at risk of the endocrine disruptive effects of these chemicals. Pharmaceutical agents, including FLX and VEN, reach aquatic ecosystems through sewage release; thus, fish could also be inadvertently affected. We report the results from a 6-day FLX exposure during early zebrafish development to an environmentally relevant level (0.54 µg/L in water) and a concentration detected in the cord blood of FLX-treated pregnant women (54 µg/L in water). The FLX exposure reduced the stress response (arithmetic difference between the stress-induced and unstressed whole-body cortisol levels) in the adult female and male zebrafish, an effect that persisted for four generations. To model the possibility of a second antidepressant exposure, filial generation 4 was exposed to VEN (5 µg/L). We found that FLX exposure sensitized these descendants to VEN. VEN treatment further suppressed cortisol production in females and decreased spawning rates in adult pairs. This is an important demonstration that in an animal model, a brief ancestral exposure of great-great-grandparents to the selective serotonin reuptake inhibitor FLX will shape the physiological responses of future generations to the serotonin and norepinephrine reuptake inhibitor VEN.

Disturbances of purinergic system in affective disorders and schizophrenia.

Purinergic system plays a role in the regulation of many psychological processes, including mood and activity. It consists of P1 receptors, with adenosine as the agonist, and P2 receptors, activated by nucleotides (e.g., adenosine 5'-triphosphate - ATP). Propounded disturbances of uric acid in affective disorders were related to the introduction of lithium for the treatment of these disorders in the 19th and 20th century. At the beginning of the 21st century, new evidence was accumulated concerning a role of uric acid in the pathogenesis and treatment of bipolar disorder (BD). In patients with BD, higher prevalence of gout and increased concentration of uric acid have been found as well as the therapeutic activity of allopurinol, used as an adjunct to mood stabilizers, has been demonstrated in mania. In recent years, the research on the role of the purinergic system in the pathogenesis and treatment of affective disorders and schizophrenia focuses on the role of adenosine (P1) receptors and nucleotide (P2) receptors. Activation of adenosine receptors is related to an antidepressant activity. Alterations of P2 receptors are also significant for the pathogenesis of affective disorders. The role of purinergic system in schizophrenia is related to the effect of adenosine and nucleotide receptors on dopaminergic and glutamatergic neurotransmission. A lot of data indicate that schizophrenia is related to a deficit of adenosine system. Changes in the purinergic system are also significant for psychopathological symptoms of schizophrenia and for the action of antipsychotic drugs.

Study design of the Routine Outcome Monitoring for Geriatric Psychiatry & Science (ROM-GPS) project; a cohort study of older patients with affective disorders referred for specialised geriatric mental health care

BackgroundAffective disorders, encompassing depressive-, anxiety-, and somatic symptom disorders, are the most prevalent mental disorders in later life. Treatment protocols and guidelines largely rely on evidence from RCTs conducted in younger age samples and ignore comorbidity between these disorders. Moreover, studies in geriatric psychiatry are often limited to the “younger old” and rarely include the most frail. Therefore, the effectiveness of treatment in routine clinical care for older patients and impact of ageing characteristics is largely unknown.ObjectiveThe primary aim of the Routine Outcome Monitoring for Geriatric Psychiatry & Science (ROM-GPS) – project is to examine the impact of ageing characteristics on the effectiveness of treatment for affective disorders in specialised geriatric mental health care.MethodsROM-GPS is a two-stage, multicentre project. In stage one, all patients aged ≥60 years referred to participating outpatient clinics for specialised geriatric mental health care will be routinely screened with a semi-structured psychiatric interview, the Mini International Neuropsychiatric Interview and self-report symptom severity scales assessing depression, generalized anxiety, hypochondria, and alcohol use. Patients with a unipolar depressive, anxiety or somatic symptom disorder will be asked informed consent to participate in a second (research) stage to be extensively phenotyped at baseline and closely monitored during their first year of treatment with remission at one-year follow-up as the primary outcome parameter. In addition to a large test battery of potential confounders, specific attention is paid to cognitive functioning (including computerized tests with the Cogstate test battery as well as paper and pencil tests) and physical functioning (including multimorbidity, polypharmacy, and different frailty indicators). The study is designed as an ongoing project, enabling minor adaptations once a year (change of instruments).DiscussionAlthough effectiveness studies using observational data can easily be biased, potential selection bias can be quantified and potentially corrected (e.g. by propensity scoring). Knowledge of age-related determinants of treatment effectiveness, may stimulate the development of new interventions. Moreover, studying late-life depressive, anxiety and somatic symptom disorders jointly enables data-driven studies for more optimal classification of these disorders in later life.Trial registrationDutch Trial Register: NL6704 (www.trialregister.nl). Retrospectively registered on 2017-12-05.