Pain and Depression: A Systematic Review IsHak, Waguih William; Wen, Raymond Y; Naghdechi, Lancer ...
Harvard review of psychiatry,
11/2018, Letnik:
26, Številka:
6
Journal Article
Recenzirano
Pain comorbid with depression is frequently encountered in clinical settings and often leads to significant impaired functioning. Given the complexity of comorbidities, it is important to address ...both pain and depressive symptoms when evaluating treatment options.
To review studies addressing pain comorbid with depression, and to report the impact of current treatments.
A systematic search of the literature databases was conducted according to predefined criteria. Two authors independently conducted a focused analysis of the full-text articles and reached a consensus on 28 articles to be included in this review.
Overall, studies suggested that pain and depression are highly intertwined and may co-exacerbate physical and psychological symptoms. These symptoms could lead to poor physical functional outcomes and longer duration of symptoms. An important biochemical basis for pain and depression focuses on serotonergic and norepinephrine systems, which is evident in the pain-ameliorating properties of serotonergic and norepinephrine antidepressants. Alternative pharmacotherapies such as ketamine and cannabinoids appear to be safe and effective options for improving depressive symptoms and ameliorating pain. In addition, cognitive-behavioral therapy may be a promising tool in the management of chronic pain and depression.
The majority of the literature indicates that patients with pain and depression experience reduced physical, mental, and social functioning as opposed to patients with only depression or only pain. In addition, ketamine, psychotropic, and cognitive-behavioral therapies present promising options for treating both pain and depression.
The objective of this review was to evaluate the efficacy of selective serotonin reuptake inhibitors (SSRIs) and SSRIs compared with other treatment modalities in preventing relapse after an episode ...of major depressive disorder (MDD). An Ovid MEDLINE and PsycINFO search (from 1987 to August 2017) was conducted using the following terms: selective serotonin reuptake inhibitors, antidepressants, depression, prevention, prophylaxis, relapse and MDD. Using predefined criteria, two authors independently selected and reached consensus on the included studies. Sixteen articles met the criteria: 10 compared the relapse rate of selective SSRIs with placebo or other SSRIs; one discussed the effectiveness of SSRIs plus psychotherapy, two compared SSRI versus tricyclic antidepressants (TCAs), two were mainly composed of TCAs plus psychotherapy, and one compared SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs). According to the included studies, the relapse risk in adults was lower when SSRIs were combined with psychotherapy. Results comparing SSRIs and SNRIs were inconclusive. TCAs may be equally as effective as SSRIs. Atypical antidepressants (mirtazapine and St John’s Wort) had no significant difference in efficacy and remission rates compared with SSRIs. Escitalopram appeared to fare better in efficacy than other SSRIs, owing to a higher prophylactic efficacy and lower side effects; however, according to the current data, this difference was not significant. To conclude, this review provides evidence that continuing SSRIs for 1 year reduces risk of MDD and relapse. Furthermore, the combination of SSRIs and cognitive behavioural therapy may effectively reduce relapse. Escitalopram appeared to yield better results and fewer side effects than did other SSRIs or SNRIs. The effectiveness in reducing relapse of SSRIs was similar to that of TCAs and atypical antidepressants.
Among patients with Parkinson's disease (PD), depression is prevalent and disabling, impacting both health outcomes and quality of life. There is a critical need for alternative pharmacological ...methods to treat PD depression, as mainstream antidepressant drugs are largely ineffective in this population. Currently, there are no recommendations for the optimal treatment of PD neuropsychiatric symptoms. Given the dual antidepressant and anti-dyskinetic effects of ketamine and other N-methyl-D-aspartate (NMDA) antagonists for PD, this review aims to examine the current evidence of NMDA antagonists for treating neuropsychiatric symptoms, including memantine, amantadine, ketamine, dizoclopine, and d-cycloserine. A comprehensive literature search was conducted using the PubMed database. We also searched the following databases up to March 1, 2018: Ovid MEDLINE, PsycINFO, CINAHL, Google Scholar, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The following keywords were used: NMDA antagonist and Parkinson's disease. Two authors independently reviewed the articles identified from the search using specific selection criteria, focusing on studies of mood, psychiatric condition, depression, cognition, and quality of life, and the consensus was reached on the 20 studies included. There is a preliminary evidence that NMDA antagonists may modulate psychiatric symptoms in PD. However, current evidence of psychiatric symptom-modifying effects is inconclusive and requires that further trials be conducted in PD. The repurposing of old NMDA antagonists, such as ketamine for depression and newer therapies, such as rapastinel, suggests that there is an emerging place for modulating the glutamatergic system for treating non-motor symptoms in PD.
•PCB153 decreased intracellular dopamine (DA) and increased (24 h) extracellular DA.•PCB153 increased DA metabolites DOPAC, DOPET, and DOPAL.•PCB95 first increased (12 h) then decreased (24 h) ...intracellular DA.•PCB95 down-regulated VMAT and GPx.•Both PCB congeners may be neurotoxic, but through different mechanisms.
Polychlorinated biphenyls (PCB) exposure at low chronic levels is a significant public health concern. Animal and epidemiological studies indicate that low PCB body burden may cause neurotoxicity and be a risk factor for neurodegenerative diseases. In the current study, we measured the ability of two non-dioxin like PCBs, 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) and 2,2′3,5′,6-pentachlorobiphenyl (PCB95), to alter dopamine (DA) levels and metabolism using the dopaminergic PC12 cell line. Our hypothesis is that treatment of PC12 cells with non-toxic concentrations of PCB153 or PCB95 for 12 and 24 h will have different effects due to different congener structures. Levels of DA and of 3,4-dihydroxyphenylacetaldehyde (DOPAL), 3, 4-dihyroxylphenylethanol (DOPET), and 3,4-dihyroxylphenylacetic acid (DOPAC) metabolite, gene expression of the dopamine synthesis enzyme tyrosine hydroxylase (TH) and the vesicular monoamine transporter (VMAT2), and gene expression of the anti-oxidant enzymes Cu/Zn and Mn superoxide oxidase (Cu/ZnSOD, MnSOD), glutathione peroxidase (GPx) and catalase were determined. PCB153 decreased intracellular and extracellular levels of DA after 12 h exposure and this was consistent with an increase in DA metabolites. After 24 h, the level of DA in medium increased compared to the control. In contrast, PCB95 exposure increased the intracellular DA level and decreased DA in medium consistent with a down-regulation of VMAT2 expression at 12 h. After 24 h exposure, PCB95 increased DA levels in media. Expression of TH mRNA increased slightly following 12 h but not at 24 h exposure. MnSOD mRNA increased up to 6–7 fold and Cu/ZnSOD increased less than two-fold after treatment with both congeners. Catalase expression was up-regulated following 24 h exposure to PCB153 and PCB95, but GPx expression was down-regulated after 12 h exposure to PCB95 only. These results suggest that PCB153 and PCB95 are neurotoxic and affect DA turnover with structure-dependent differences between these two congeners.
•Phenolic and sulfated metabolites of PCBs 3, 8, 11, and 52 were studied in vitro.•The OH-PCBs displayed toxicity to N27, SHSY-5Y, and HepG2 cells.•OH-PCBs were generally more toxic than the ...corresponding PCBs or PCB sulfates.•4-PCB 52 sulfate, however, showed significant toxicity to neural and hepatic cells.•Mechanisms for 4-PCB 52 sulfate toxicity may require its metabolism to 4-OH-PCB 52.
Although neurotoxicity and hepatotoxicity have long been associated with exposure to polychlorinated biphenyls (PCBs), less is known about the selective toxicity of those hydroxylated PCBs (OH-PCBs) and PCB sulfates that are metabolites derived from exposure to PCBs found in indoor air. We have examined the toxicity of OH-PCBs and PCB sulfates derived from PCBs 3, 8, 11, and 52 in two neural cell lines (N27 and SH-SY5Y) and an hepatic cell line (HepG2). With the exception of a similar toxicity seen for N27 cells exposed to either OH-PCB 52 or PCB 52 sulfate, these OH-PCBs were more toxic to all three cell-types than their corresponding PCB or PCB sulfate congeners. Differences in the distribution of individual OH-PCB and PCB sulfate congeners between the cells and media, and the ability of cells to interconvert PCB sulfates and OH-PCBs, were important components of cellular sensitivity to these toxicants.
The aldehyde metabolite of dopamine, 3,4-dihydroxyphenylacetaldehyde (DOPAL) is an endogenous neurotoxin implicated in Parkinson's Disease. Elucidating protein targets of DOPAL is essential in ...understanding it's pathology. The enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a target of DOPAL.
GAPDH activity was measured via reduction of NAD+ cofactor (340 nm). Protein aggregation was assessed with SDS-PAGE methods and specific modification via chemical probes.
Low micromolar levels of DOPAL caused extensive GAPDH aggregation and irreversibly inhibited enzyme activity. The inactivation of GAPDH was dependent on both the catechol and aldehyde moieties of DOPAL. It is suggested that Cys are modified and oxidized by DOPAL.
The mechanism by which DOPAL modifies GAPDH can serve as a mechanistic explanation to the pathological events in Parkinson's Disease.
•DOPAL caused GAPDH oligomerization in a time and dose-dependent manner.•GAPDH activity was irreversibly inhibited at low micromolar levels of DOPAL.•Inhibition of activity was dependent on the catechol and aldehyde of DOPAL.•It is suggested that DOPAL modifies Cys residues by oxidation of free thiols.
Summary The neurotransmitter dopamine (DA) is important for numerous biological functions, including control of movement. Oxidation of DA to highly toxic and reactive species has been hypothesized to ...contribute to the selective neurodegeneration observed in Parkinson's disease (PD). DA catabolism is initiated by oxidative deamination via monoamine oxidase to yield 3,4-dihydroxyphenylacetaldehyde (DOPAL). Such metabolism can be problematic as it greatly increases the toxicity of DA by production of DOPAL, known to be a toxic and reactive intermediate. DOPAL undergoes carbonyl metabolism primarily via aldehyde dehydrogenase (ALDH) enzymes to a less toxic acid product. Previous studies from our laboratory have shown that cellular ALDH enzymes are sensitive towards products of oxidative stress and lipid peroxidation, which are thought to be elevated during PD pathogenesis. Inhibition of ALDH and the resulting accumulation of DOPAL are concerning as DOPAL is toxic to dopaminergic cells, readily modifies proteins and causes protein aggregation. In addition, pesticides with association between exposure and PD incidence can interfere with DA metabolism and trafficking and/or ALDH activity, directly or indirectly, yielding elevation of DOPAL. Therefore, impairment of carbonyl metabolism is a potential mechanistic link between cellular insult and generation of a toxic and reactive intermediate endogenous to dopamine neurons.
Heart Failure is a chronic syndrome affecting over 5.7 million in the US and 26 million adults worldwide with nearly 50% experiencing depressive symptoms. The objective of the study is to compare the ...effects of two evidence-based treatment options for adult patients with depression and advanced heart failure, on depressive symptom severity, physical and mental health related quality of life (HRQoL), heart-failure specific quality of life, caregiver burden, morbidity, and mortality at 3, 6 and 12-months.
Trial design. Pragmatic, randomized, comparative effectiveness trial. Interventions. The treatment interventions are: (1) Behavioral Activation (BA), a patient-centered psychotherapy which emphasizes engagement in enjoyable and valued personalized activities as selected by the patient; or (2) Antidepressant Medication Management administered using the collaborative care model (MEDS). Participants. Adults aged 18 and over with advanced heart failure (defined as New York Heart Association (NYHA) Class II, III, and IV) and depression (defined as a score of 10 or above on the PHQ-9 and confirmed by the MINI International Neuropsychiatric Interview for the DSM-5) selected from all patients at Cedars-Sinai Medical Center who are admitted with heart failure and all patients presenting to the outpatient programs of the Smidt Heart Institute at Cedars-Sinai Medical Center. We plan to randomize 416 patients to BA or MEDS, with an estimated 28% loss to follow-up/inability to collect follow-up data. Thus, we plan to include 150 in each group for a total of 300 participants from which data after randomization will be collected and analyzed.
The current trial is the first to compare the impact of BA and MEDS on depressive symptoms, quality of life, caregiver burden, morbidity, and mortality in patients with depression and advanced heart failure. The trial will provide novel results that will be disseminated and implemented into a wide range of current practice settings.
ClinicalTrials.Gov Identifier: NCT03688100.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PurposeDetermination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND).MethodsFifty GAND subjects were evaluated to determine consistent genotypic/phenotypic ...features. Immunoprecipitation assays utilizing in vitro transcription–translation products were used to evaluate GATAD2B missense variants’ ability to interact with binding partners within the nucleosome remodeling and deacetylase (NuRD) complex.ResultsSubjects had clinical findings that included macrocephaly, hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios, apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novelGATAD2B variants were identified with multiple variant types (nonsense, truncating frameshift, splice-site variants, deletions, and missense). Seven subjects were identified with missense variants that localized within two conserved region domains (CR1 or CR2) of the GATAD2B protein. Immunoprecipitation assays revealed several of these missense variants disrupted GATAD2B interactions with its NuRD complex binding partners.ConclusionsA consistent GAND phenotype was caused by a range of genetic variants in GATAD2B that include loss-of-function and missense subtypes. Missense variants were present in conserved region domains that disrupted assembly of NuRD complex proteins. GAND’s clinical phenotype had substantial clinical overlap with other disorders associated with the NuRD complex that involve CHD3 and CHD4, with clinical features of hypotonia, intellectual disability, cardiac defects, childhood apraxia of speech, and macrocephaly.
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