Major Depressive Disorder and Heroin-dependent Patients Share Decreased Frontal Gray Matter Volumes: A Voxel-Based Morphometry Study (original) (raw)
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Bidirectional relationship between heroin addiction and depression: Behavioural and neural studies
2020
Heroin is highly addictive drug that users use in spite of its negative consequences. Many research on drug dependence, persistence and relapse confirmed that there is a relationship between drug addiction and negative mood states. The present review article investigated the relationship between depression, negative mood, and drug abuse. In addition, the article investigated. The relationship between depression, anxiety, and negative mood-induced heroin-seeking behavior. Previous studies pointed out that depression symptoms could be as a result of heroin use, persistence, and relapse and should be considered in the assessment and treatment of heroin addiction. The greater severity attributable to comorbidity suggests that addressing depression and substance use is a complex and poses an increased challenge for treatment, recovery and abstinence.
Cerebral metabolism and mood in remitted opiate dependence
Drug and Alcohol Dependence, 2007
Background-Opiate-dependent individuals are prone to dysphoria that may contribute to treatment failure. Methadone-maintenance therapy (MMT) may mitigate this vulnerability, but controversy surrounds its long-term use. Little is known about the neurobiology of mood dysregulation in individuals receiving or removed from MMT.
Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity
Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroindependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehiclecontrolled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in heroin-dependent patients and to quantify the efficacy of maintenance treatments in drug addiction.
Resting-state Abnormalities in Heroin-dependent Individuals
Drug addiction is a major health problem worldwide. Recent neuroimaging studies have shed light into the underlying mechanisms of drug addiction as well as its consequences to the human brain. The most vulnerable , to heroin addiction, brain regions have been reported to be specific prefrontal, parietal, occipital, and temporal regions, as well as, some subcortical regions. The brain regions involved are usually linked with reward, motivation/drive, memory/learning, inhibition as well as emotional control and seem to form circuits that interact with each other. So, along with neuroimaging studies, recent advances in resting-state dynamics might allow further assessments upon the multilayer complexity of addiction. In the current manuscript, we comprehensively review and discuss existing resting-state neuroimaging findings classified into three overlapping and interconnected groups: functional connectivity alterations, structural deficits and abnormal topological properties. Moreover , behavioral traits of heroin-addicted individuals as well as the limitations of the currently available studies are also reviewed. Finally, in need of a contemporary therapy a multimodal therapeutic approach is suggested using classical treatment practices along with current neurotechonologies, such as neurofeedback and goal-oriented video-games.
Neurophotonics, 2018
Many patients with substance use disorders (SUDs) live in a stressful environment, and comorbidity is not uncommon. Understanding the neural mechanisms underlying heroin and nicotine dependences and their relationships to social cognition could facilitate behavioral therapy efficacy. We aimed to provide a translational approach that leads to identifying potential biomarkers for opioid use disorder (OUD) susceptibility during recovery. We examined the clinical characters and the relationships between theory of mind (ToM) and executive functions in three groups: heroin plus nicotine-dependent (HND) patients who had remained heroin abstinent (≥3 months), nicotine-dependent (ND) subjects, and healthy controls (C). The domains included emotion recognition, inhibition, shifting, updating, access, and processing speed. Resting-state functional connectivity (rsFC), ToM task-induced functional connectivity, and brain networks were then explored among 21 matched subjects using functional near-infrared spectroscopy. HND enhanced the severities of anxiety, depression, and hyperactivity. Inhibition domain was impaired in both HND and ND. No impairment in domains of emotion recognition, access, and update was observed. HND demonstrated enhanced rsFC in the medial prefrontal cortex and orbitofrontal cortex (OFC) and decreased ToM-induced connectivity across the PFC. The right superior frontal gyrus in the OFC (oSFG; x ¼ 22, y ¼ 77, and z ¼ 6) was associated with working memory and emotion recognition in HND. Using a neuroimaging tool, these results supported the prominent reward-deficit-and-stresssurfeit hypothesis in SUDs, especially OUD, after protracted withdrawal. This may provide an insight in identifying potential biomarkers related to a dynamic environment.
Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse.
NeuroImage, 2004
Thirty male Sprague -Dawley rats were divided into two groups and trained to self-administer either saline (n = 14) or heroin (0.1 mg/kg per injection, n = 16) for 10 -12 days until a stable self-administration (SA) behavior was achieved. After 8 -9 days of withdrawal, each group was divided into two subgroups for reinstatement tests and functional magnetic resonance image (fMRI) scanning, respectively, to determine the neural correlates of the reinstatement of heroin-seeking behavior. For reinstatement testing, heroin-SA rats (n = 10) displayed robust reinstatement of drug-seeking behavior triggered by an acute heroin priming injection, whereas saline control rats (n = 8) did not show such a behavioral response. Regional positive or negative blood oxygen level-dependent (BOLD) signals, induced by heroin priming injection, were observed in both groups of rats during fMRI scanning. However, such heroin-induced positive BOLD signal primarily in the prefrontal cortex and parietal cortex was significantly attenuated in heroin-SA rats (n = 6) when compared to saline control rats (n = 6). Similarly, the heroin-induced negative BOLD signal in the subcortical regions, such as in the nucleus accumbens and hippocampus, was also significantly attenuated in both signal intensity and number of brain voxels activated in heroin-SA rats. These data demonstrate that heroininduced reinstatement of drug-seeking behavior coincides with a significant, enduring reduction in opiate-induced brain activity in heroin-SA rats, suggesting a possible role of opiate tolerance in mediating reinstatement of drug-seeking behavior. D
Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression
Journal of Clinical Investigation, 2013
Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid cortex (PAC) in both heroin abusers and MDD subjects. Similar to humans, rats that chronically self-administered heroin had reduced Pdyn mRNA expression in the PAC at a time point associated with a negative affective state. Using the in vivo functional imaging technology DREAMM (DREADD-assisted metabolic mapping, where DREADD indicates designer receptors exclusively activated by designer drugs), we found that selective inhibition of Pdyn-expressing neurons in the rat PAC increased metabolic activity in the extended amygdala, which is a key substrate of the extrahypothalamic brain stress system. In parallel, PAC-specific Pdyn inhibition provoked negative affect-related physiological and behavioral changes. Altogether, our translational study supports a functional role for impaired Pdyn in the PAC in opiate abuse through activation of the stress and negative affect neurocircuitry implicated in addiction vulnerability. Conflict of interest: The authors have declared that no conflict of interest exists.