Mclntyre reflects on a study by Watson et al which is very prescient in its integration of prediction, prevention, deep in vivo phenotyping, the parsing of disease mechanisms and models of major ...depressive disorder. Using data from the Netherlands Study of Depression and Anxiety (NESDA) cohort, the investigators sought to determine whether surrogate measures of insulin resistance were predictive of incident PSM-IV-defined major depressive disorder in a well-characterized cohort of individuals without a current or lifetime history of depression or anxiety disorders.
While there is clearly an association between improvement in depressive symptoms and functioning, symptom improvement can also be dissociated from functional improvement and work loss.3,4 Hence there ...has been increasing recognition that symptomatic remission is an insufficient goal of treatment for MDD and that return to premorbid psychosocial functioning should be targeted.5 Cognitive dysfunction refers to deficits in attention, verbal and nonverbal learning, short-term and working memory, visual and auditory processing, problem solving, processing speed, and motor functioning. Numerous pharmacotherapy augmentation strategies have shown efficacy in MDD, including lithium52 and atypical APs,53 but cognitive dysfunction has not been specifically examined in these studies. ...there is evidence that lithium is associated with adverse cognitive side effects that may negatively impact psychosocial functioning.54 Likewise, there is evidence to suggest that, in BD, atypical APs may worsen cognitive performance.55,56 Psychostimulants may be expected to have positive effects on cognition, but augmentation studies of osmotic-release oral system-methylphenidate57,58 and lisdexamfetamine59,60 in MDD have shown inconsistent results on depressive symptoms and subjective neurocognitive measures, although the latter were not always measured.
Bipolar disorder (BD) is strongly associated with immune dysfunction. Replicated epidemiological studies have demonstrated that BD has high rates of inflammatory medical comorbidities, including ...autoimmune disorders, chronic infections, cardiovascular disease and metabolic disorders. Cytokine studies have demonstrated that BD is associated with chronic low-grade inflammation with further increases in pro-inflammatory cytokine levels during mood episodes. Several mechanisms have been identified to explain the bidirectional relationship between BD and immune dysfunction. Key mechanisms include cytokine-induced monoamine changes, increased oxidative stress, pathological microglial over-activation, hypothalamic-pituitary-adrenal (HPA) axis over-activation, alterations of the microbiome-gut-brain axis and sleep-related immune changes. The inflammatory-mood pathway presents several potential novel targets in the treatment of BD. Several proof-of-concept clinical trials have shown a positive effect of anti-inflammatory agents in the treatment of BD; however, further research is needed to determine the clinical utility of these treatments. Immune dysfunction is likely to only play a role in a
of BD patients and as such, future clinical trials should also strive to identify which specific group(s) of BD patients may benefit from anti-inflammatory treatments.
This meta-analysis aimed to estimate the global lifetime and 12-month prevalence of suicidal behavior, deliberate self-harm and non-suicidal self-injury in children and adolescents.
A systematic ...search for relevant articles published between 1989 to 2018 was performed in multiple electronic databases. The aggregate 12-month and lifetime prevalence of suicidal behavior, deliberate self-harm, and non-suicidal self-injury were calculated based on the random-effects model. Subgroup analyses were performed to compare the prevalence according to school attendance and geographical regions.
: A total of 686,672 children and adolescents were included. The aggregate lifetime and 12-month prevalence of suicide attempts was 6% (95% CI: 4.7-7.7%) and 4.5% (95% CI: 3.4-5.9%) respectively. The aggregate lifetime and 12-month prevalence of suicidal plan was 9.9% (95% CI: 5.5-17%) and 7.5% (95% CI: 4.5-12.1%) respectively. The aggregate lifetime and 12-month prevalence of suicidal ideation was 18% (95% CI: 14.2-22.7%) and 14.2% (95% CI: 11.6-17.3%) respectively. The aggregate lifetime and 12-month prevalence of non-suicidal self-injury was 22.1% (95% CI: 16.9-28.4%) and 19.5% (95% CI: 13.3-27.6%) respectively. The aggregate lifetime and 12-month prevalence of deliberate self-harm was 13.7% (95% CI: 11.0-17.0%) and 14.2% (95% CI: 10.1-19.5%) respectively. Subgroup analyses showed that full-time school attendance, non-Western countries, low and middle-income countries, and geographical locations might contribute to the higher aggregate prevalence of suicidal behaviors, deliberate self-harm, and non-suicidal self-injury.
: This meta-analysis found that non-suicidal self-injury, suicidal ideation, and deliberate self-harm were the three most common suicidal and self-harm behaviors in children and adolescents.
McIntyre et al respond to the comments regarding their article on ketamine. They explain that the contributors to their article "Synthesizing the Evidence for Ketamine and Esketamine in ...Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation" were identified and invited by the first and last author. Invitation was sent to experts on the basis of their expertise in mood disorders, psychopharmacology, neurobiology of mood disorders, rapid-acting antidepressants, ketamine/esketamine and derivatives, or implementation experience. They also agree that there is a range of somatic treatment options for adults with treatment-resistant depression, and they describe in large measure the range of options noted by Dr. Mattes.
•Levels of anxiety, depression, stress and insomnia were higher in psychiatric patients.•Psychiatric patients had more health concerns, impulsivity and suicidal ideation.•More than one-third of ...psychiatric patients fulfil the diagnostic criteria for PTSD.•Poor physical health was associated with higher levels of anxiety, depression and stress.•The above findings have service and research implications for immunopsychiatry.
This study aimed to assess and compare the immediate stress and psychological impact experienced by people with and without psychiatric illnesses during the peak of 2019 coronavirus disease (COVID-19) epidemic with strict lockdown measures. Seventy-six psychiatric patients and 109 healthy control subjects were recruited from Chongqing, China and completed a survey on demographic data, physical symptoms during the past 14 days and a range of psychiatric symptoms using the Impact of Event Scale-Revised (IES-R), Depression, Anxiety and Stress Scale (DASS-21) and Insomnia Severity Index (ISI). IES-R measures PTSD symptoms in survivorship after an event. DASS-21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. The mean IES-R, DASS-21 anxiety, depression and stress subscale and ISI scores were higher in psychiatric patients than healthy controls (p < 0.001). Serious worries about their physical health, anger and impulsivity and intense suicidal ideation were significantly higher in psychiatric patients than healthy controls (p < 0.05). More than one-third of psychiatric patients might fulfil the diagnostic criteria post-traumatic stress disorder (PTSD). More than one-quarter of psychiatric patients suffered from moderately severe to severe insomnia. Respondents who reported no change, poor or worse physical health status and had a psychiatric illness were significantly more likely to have higher mean IES-R, DASS depression, anxiety and stress subscale scores and ISI scores (p < 0.05). This study confirms the severity of negative psychological impact on psychiatric patients during the COVID-19 epidemic with strict lockdown measures. Understanding the psychological impact on psychiatric patients during the COVID-19 pandemic has the potential to provide insight into how to develop a new immunopsychiatry service. Further research is required to compare pro-inflammatory cytokines between psychiatric patients and healthy controls during the pandemic.
Mood disorders have been recognized by the World Health Organization (WHO) as the leading cause of disability worldwide. Notwithstanding the established efficacy of conventional mood agents, many ...treated individuals continue to remain treatment refractory and/or exhibit clinically significant residual symptoms, cognitive dysfunction, and psychosocial impairment. Therefore, a priority research and clinical agenda is to identify pathophysiological mechanisms subserving mood disorders to improve therapeutic efficacy.
During the past decade, inflammation has been revisited as an important etiologic factor of mood disorders. Therefore, the purpose of this synthetic review is threefold: 1) to review the evidence for an association between inflammation and mood disorders, 2) to discuss potential pathophysiologic mechanisms that may explain this association and 3) to present novel therapeutic options currently being investigated that target the inflammatory–mood pathway.
Accumulating evidence implicates inflammation as a critical mediator in the pathophysiology of mood disorders. Indeed, elevated levels of pro-inflammatory cytokines have been repeatedly demonstrated in both major depressive disorder (MDD) and bipolar disorder (BD) patients. Further, the induction of a pro-inflammatory state in healthy or medically ill subjects induces ‘sickness behavior’ resembling depressive symptomatology.
Potential mechanisms involved include, but are not limited to, direct effects of pro-inflammatory cytokines on monoamine levels, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, pathologic microglial cell activation, impaired neuroplasticity and structural and functional brain changes.
Anti-inflammatory agents, such as acetyl-salicylic acid (ASA), celecoxib, anti-TNF-α agents, minocycline, curcumin and omega-3 fatty acids, are being investigated for use in mood disorders. Current evidence shows improved outcomes in mood disorder patients when anti-inflammatory agents are used as an adjunct to conventional therapy; however, further research is needed to establish the therapeutic benefit and appropriate dosage.
•Inflammation and mood disorders have a bidirectional interaction.•Cytokines, monoamines, the HPA axis and microglial cells are key players involved.•Anti-inflammatory agents show promise for use in the treatment of mood disorders.
Individuals with bipolar disorder (BD) have a higher prevalence of obesity and metabolic syndrome (MetS) compared with the general population. Obesity and MetS are associated with cognitive deficits ...and brain imaging abnormalities in the general population. Obesity and components of MetS might potentially associate with neuroimaging and neurocognitive findings in BD.
A literature search of studies investigating the association between obesity (and other components of MetS) and neurocognitive and neuroimaging findings in BD was conducted. In addition to a systematic review, a random-effects meta-analysis was conducted when sufficient data were available.
Twenty-three studies were included in the current systematic review. Overweight/obese patients were significantly associated with impaired neurocognition compared normal weight individuals with BD (d = 0.37). The most robust association between obesity and cognitive deficits in BD was observed in the cognitive subdomain of executive functions (d = 0.61). There was also evidence for a significant relationship between cognitive impairment in BD and other components of MetS including hypertension, dyslipidemia, and diabetes. Overweight/obese individuals with BD had more pronounced brain imaging abnormalities than normal weight individuals with BD.
Obesity and related cardiovascular risk factors significantly are associated with more severe cognitive and brain imaging abnormalities in BD. Medical co-morbidities can potentially contribute to functional decline observed in some patients throughout the course of BD.
Obesity and mood disorders are highly prevalent and co-morbid. Epidemiological studies have highlighted the public health relevance of this association, insofar as both conditions and its ...co-occurrence are associated with a staggering illness-associated burden. Accumulating evidence indicates that obesity and mood disorders are intrinsically linked and share a series of clinical, neurobiological, genetic and environmental factors. The relationship of these conditions has been described as convergent and bidirectional; and some authors have attempted to describe a specific subtype of mood disorders characterized by a higher incidence of obesity and metabolic problems. However, the nature of this association remains poorly understood. There are significant inconsistencies in the studies evaluating metabolic and mood disorders; and, as a result, several questions persist about the validity and the generalizability of the findings. An important limitation in this area of research is the noteworthy phenotypic and pathophysiological heterogeneity of metabolic and mood disorders. Although clinically useful, categorical classifications in both conditions have limited heuristic value and its use hinders a more comprehensive understanding of the association between metabolic and mood disorders. A recent trend in psychiatry is to move toward a domain specific approach, wherein psychopathology constructs are agnostic to DSM-defined diagnostic categories and, instead, there is an effort to categorize domains based on pathogenic substrates, as proposed by the National Institute of Mental Health (NIMH) Research Domain Criteria Project (RDoC). Moreover, the substrates subserving psychopathology seems to be unspecific and extend into other medical illnesses that share in common brain consequences, which includes metabolic disorders. Overall, accumulating evidence indicates that there is a consistent association of multiple abnormalities in neuropsychological constructs, as well as correspondent brain abnormalities, with broad-based metabolic dysfunction, suggesting, therefore, that the existence of a "metabolic-mood syndrome" is possible. Nonetheless, empirical evidence is necessary to support and develop this concept. Future research should focus on dimensional constructs and employ integrative, multidisciplinary and multimodal approaches.
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