Bipolar disorder and substance misuse: pathological and therapeutic implications of their comorbidity and cross-sensitisation

BackgroundBipolar disorder has a high co-occurrence with substance use disorders, but the pathophysiological mechanisms have not been adequately explored.AimsTo review the role of stress in the onset and recurrence of affective episodes and substance misuse.MethodWe review the mechanisms involved in sensitisation (increased responsivity) to recurrence of stressors, mood episodes and cocaine use.ResultsEvidence suggests that intermittent stressors, mood episodes and bouts of cocaine use not only show sensitisation to themselves, but cross-sensitisation to the others contributing to illness progression. Converseley, an understanding of the common mechanisms of sensitisation (such as regionally selective alterations in brain derived neurotrophic factor (BDNF) and hyperactivity of striatally based habit memories), could also result in single therapies (such as N-acetylcysteine) having positive effects in all three domains.ConclusionsThese interacting sensitisation processes suggest the importance of early intervention in attempting to prevent increasingly severe manifestations of bipolar illness and substance misuse progression.

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Depression as a Recurrent, Progressive Illness

10.1093/med/9780190603342.003.0003 ◽

2018 ◽

Cited By ~ 1

Author(s):

Robert M. Post

Keyword(s):

Bipolar Disorder ◽

Behavioral Sensitization ◽

Clinical Intervention ◽

The United States ◽

The Body ◽

Childhood Onset ◽

Bipolar Illness ◽

Specific Memory ◽

Illness Progression

Clinical Highlights and summary of Chapter• Episodes of depression and bipolar illness progress in two ways:faster recurrences as a function of number of prior episodes, andgreater autonomy (decreased need for precipitation by stressors(Episode Sensitization)• Recurrent stressors result in increased reactivity to subsequent stressors(Stress sensitization) and bouts of stimulant abuse increase in severity with repetition(Stimulant-induced behavioral sensitization)• Each type of sensitization cross-sensitizes to the others and drives illness progression• Each type of sensitization involves specific memory-like epigenetic processes as well as nonspecific cellular toxicities• Childhood onset depression and bipolar illness have a more adverse course than adult onset illness and are increasing in incidence via a cohort (year of birth) effect• As opposed to genetic vulnerability, each type of sensitization can be prevented with appropriate clinical intervention and prevention, which should lessen illness severity and progression• Seeing depression and bipolar disorder as progressive illnesses changes the therapeutic emphasis away from acute treatment and instead to long term prophylaxis• Preventing recurrent depressions will likely protect the brain, the body, and the personWord count with Named refs = 6,417>Depression and bipolar disorder are illnesses which tend to progress with each new recurrence. Stressors, mood episodes, and bouts of substance abuse each sensitize (show increased reactivity) upon their repetition and cross-sensitization to the others. These sensitization processes appear to have a memory-like and epigenetic basis, in some instances conveying lifelong increased vulnerability to illness recurrence and progression. Greater numbers of episodes are associated with faster recurrences, lesser need for stress precipitation, cognitive dysfunction, pathological changes in brain, treatment refractoriness, and loss of many years of life expectancy, predominantly from cardiovascular disease. Such a perspective emphasizes the need for greater awareness of higher incidence of psychiatric and medical comorbidities in the United States compared to many European countries, and the need for earlier intervention and more sustained long term prophylaxis to prevent illness progression and its adverse consequences on brain and body.

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Demographic and Mental Health Characteristics of Individuals Who Present to Community Health Clinics With Substance Misuse

Health Services Research and Managerial Epidemiology ◽

10.1177/2333392817734523 ◽

2017 ◽

Vol 4 ◽

pp. 233339281773452 ◽

Cited By ~ 4

Author(s):

Praise O. Iyiewuare ◽

Colleen McCullough ◽

Allison Ober ◽

Kirsten Becker ◽

Karen Osilla ◽

...

Keyword(s):

Mental Health ◽

Bipolar Disorder ◽

Substance Use ◽

Community Health ◽

Substance Misuse ◽

Substance Use Treatment ◽

Prescription Opioid ◽

Opioid Misuse ◽

Health Clinics ◽

Community Health Clinics

Introduction: Community health clinics (CHCs) are an opportune setting to identify and treat substance misuse. This study assessed the characteristics of patients who presented to a CHC with substance misuse. Methods: Personnel at a large CHC administered a 5-question screener to patients between June 3, 2014, and January 15, 2016, to assess past 3-month alcohol use, prescription opioid misuse, or illicit drug use. We stratified screen-positive patients into 4 diagnostic groups: (1) probable alcohol use disorder (AUD) and no comorbid opioid use disorder (OUD); (2) probable heroin use disorder; (3) probable prescription OUD, with or without comorbid AUD; and (4) no probable substance use disorder. We describe substance use and mental health characteristics of screen-positive patients and compare the characteristics of patients in the diagnostic groups. Results: Compared to the clinic population, screen-positive patients (N = 733) included more males ( P < .0001) and had a higher prevalence of probable bipolar disorder ( P < .0001) and schizophrenia ( P < .0001). Eighty-seven percent of screen-positive patients had probable AUD or OUD; only 7% were currently receiving substance use treatment. The prescription opioid and heroin groups had higher rates of past bipolar disorder and consequences of mental health conditions than the alcohol only or no diagnosis groups ( P < .0001). Conclusions: Patients presenting to CHCs who screen positive for alcohol or opioid misuse have a high likelihood of having an AUD or OUD, with or without a comorbid serious mental illness. Community health clinics offering substance use treatment may be an important resource for addressing unmet need for substance use treatment and comorbid mental illness.

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THE ROLE OF THE EUROPEAN AGRICULTURAL FUNDING IN BULGARIA

Economics Profession Business ◽

10.14258/epb201965 ◽

2020 ◽

pp. 95-101

Author(s):

Ognyan Stoichkova

Keyword(s):

European Union ◽

Agricultural Policy ◽

Agricultural Sector ◽

The European Union ◽

Agricultural Industry ◽

Positive Effects ◽

The Common ◽

Programming Period ◽

The Eu

The article deals with the issues related to financing of agricultural industry in Bulgaria from the EU funds and programs. The outcomes of European support under the first and second pillars of the Common Agricultural Policy of the European Union, in which Bulgaria has been participating since 2007, are analyzed. Besides, the positive effects on Bulgaria’s agriculture as well as the problems facing the agricultural sector in the new programming period are highlighted.

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The Potential Role of the NLRP3 Inflammasome as a Link between Mitochondrial Complex I Dysfunction and Inflammation in Bipolar Disorder

Neural Plasticity ◽

10.1155/2015/408136 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 19

Author(s):

Helena Kyunghee Kim ◽

Wenjun Chen ◽

Ana Cristina Andreazza

Keyword(s):

Bipolar Disorder ◽

Nlrp3 Inflammasome ◽

Complex I ◽

Potential Role ◽

Mitochondrial Complex I ◽

Mitochondrial Complex ◽

Therapeutic Implications ◽

Pyrin Domain ◽

Redox Sensor

Mitochondrial dysfunction and activation of the inflammatory system are two of the most consistently reported findings in bipolar disorder (BD). More specifically, altered levels of inflammatory cytokines and decreased levels of mitochondrial complex I subunits have been found in the brain and periphery of patients with BD, which could lead to increased production of mitochondrial reactive oxygen species (ROS). Recent studies have shown that mitochondrial production of ROS and inflammation may be closely linked through a redox sensor known as nod-like receptor pyrin domain-containing 3 (NLRP3). Upon sensing mitochondrial release of ROS, NLRP3 assembles the NLRP3 inflammasome, which releases caspase 1 to begin the inflammatory cascade. In this review, we discuss the potential role of the NLRP3 inflammasome as a link between complex I dysfunction and inflammation in BD and its therapeutic implications.

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Psychopharmacology of substance misuse and comorbid psychiatric disorders

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2004.0061.x ◽

2004 ◽

Vol 16 (1) ◽

pp. 19-25 ◽

Cited By ~ 5

Author(s):

M. T. Abou-Saleh

Keyword(s):

Psychiatric Disorders ◽

Mood Disorders ◽

Substance Misuse ◽

Psychotic Disorders ◽

Psychological Treatment ◽

Common Occurrence ◽

Dual Disorders ◽

The Common ◽

Psychosocial Approaches

The common occurrence of comorbid substance misuse and other psychiatric disorders has challenged the diagnostic and therapeutic skills of professionals concerned with the care of patients with these dual disorders. Combined pharmacological and psychological treatment approaches have evolved empirically drawing upon standard treatments with emphasis on psychosocial approaches to substance misuse for psychotic disorders and pharmacological approaches for mood disorders. Advances in the biology of both disorders have started to inform their psychopharmacology. The specific role of atypical antipscychotics is highlighted. Further studies of the biology of comorbidity will impact the use of effective pharmaceuticals such as clozapine with dual effects on schizophrenia and substance misuse.

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The Role of Kynurenines in Cognitive Dysfunction in Bipolar Disorder

Neuropsychobiology ◽

10.1159/000520152 ◽

2021 ◽

pp. 1-8

Author(s):

Kaat Hebbrecht ◽

Manuel Morrens ◽

Erik J. Giltay ◽

Alexander L.N. van Nuijs ◽

Bernard Sabbe ◽

...

Keyword(s):

Bipolar Disorder ◽

Cognitive Functioning ◽

Processing Speed ◽

Verbal Memory ◽

Large Scale ◽

Bipolar Depression ◽

Low Grade ◽

Therapeutic Implications ◽

Depression Group

Introduction: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway metabolites are key inflammatory mediators, studies investigating the association between KYN metabolism and cognition in BD are scarce. We aimed to explore the relationship between KYN metabolism and cognitive functioning across different mood states in BD. Methods: Sixty-seven patients with BD (35 depressed and 32 [hypo] manic) and 29 healthy controls were included. Cognitive functioning was assessed at 3 time intervals (baseline, 4, and 8 months) assessing processing speed, sustained attention, verbal memory, working memory, and response inhibition. Plasma samples for quantification of 3-hydroxykynurenine, quinolinic acid, and kynurenic acid (KYNA) were concurrently provided. Linear mixed models were used for statistical analysis. Results: The manic group showed deficits in all assessed cognitive domains with the exception of verbal memory at all test moments. The bipolar depression group showed deficits in the processing speed at all test moments. Throughout the whole follow-up period, KYNA was significantly lower in both patient groups than in controls. Only in the bipolar depression group, low KYNA was associated with worse global cognitive functioning (B = 0.114, p = 0.02) and slower processing speed in particular (B = 0.139, p = 0.03). Conclusion: Only in the bipolar depression group, lower KYNA was associated with worse cognitive functioning. Future large-scale longitudinal studies are warranted to confirm the role of KYN metabolites in cognitive impairment in patients with BD and the possible therapeutic implications of this relationship.

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