Opioid use in the United States has steadily risen since the 1990s, along with staggering increases in addiction and overdose fatalities. With this surge in prescription and illicit opioid abuse, it is paramount to understand the genetic risk factors and neuropsychological effects of opioid use disorder (OUD). Polymorphisms disrupting the opioid and dopamine systems have been associated with increased risk for developing substance use disorders. Molecular imaging studies have revealed how these polymorphisms impact the brain and contribute to cognitive and behavioral differences across individuals. Here, we review the current molecular imaging literature to assess how genetic variations in the opioid and dopamine systems affect function in the brain's reward, cognition, and stress pathways, potentially resulting in vulnerabilities to OUD. Continued research of the functional consequences of genetic variants and corresponding alterations in neural mechanisms will inform prevention and treatment of OUD.

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Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders.

Cerebellar dysfunction plays a critical role in neurodevelopmental disorders with long-term behavioral and neuropsychiatric symptoms. A 43-year-old woman with a cerebellum arteriovenous malformation and history of behavioral dysregulation since childhood is described. After the rupture of the cerebellar malformation in adulthood, her behavior morphed into specific psychiatric symptoms and cognitive deficits occurred. The neuropsychological assessment evidenced impaired performance in attention, visuospatial, memory, and language domains. Moreover, psychiatric assessment indicated a borderline personality disorder. Brain MRI examination detected macroscopic abnormalities in the cerebellar posterior lobules VI, VIIa (Crus I), and IX, and in the posterior area of the vermis, regions usually involved in cognitive and emotional processing. The described patient suffered from cognitive and behavioral symptoms that are part of the cerebellar cognitive affective syndrome. This case supports the hypothesis of a cerebellar role in personality disorders emphasizing the importance of also examining the cerebellum in the presence of behavioral disturbances in children and adults.

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Development of a Psychiatric Disorder Linked to Cerebellar Lesions

Risk taking, sensation seeking and personality as related to changes in substance use from adolescence to young adulthood.

The interaction between biological and environmental factors (especially adverse childhood experiences, ACEs) plays a crucial role in the development and maintenance of borderline personality disorder (BPD). These factors act influencing BPD core features such as pervasive instability in affect regulation, impulse control, social cognition, and interpersonal relationships. In line with this perspective, abnormalities in social cognition and related neurobiological underpinnings could mediate the relationship between ACEs and psychopathological manifestations in adulthood. In a sample of 14 females, functional connectivity (FC) analyses were performed modeling the interaction between ACEs and corticolimbic dysregulation during emotional processing and its relationship with BPD symptom severity. ACEs were associated with a dampening of the negative FC between (1) the right amygdala (Amy) and right dorsolateral prefrontal cortex (DLPFC) and between (2) the left Amy and bilateral DLPFC, right precuneus, left cerebellum and left dorsomedial prefrontal cortex during emotional processing. The connectivity between right Amy and DLPFC mediates the relationship between childhood adversities and BPD symptomatology. Furthermore, the negative FC between Amy and DLPFC, postcentral gyrus, the vermis of cerebellum and precuneus was also associated with BPD symptom severity, with a weaker negative coupling between Amy and these regions being related to a worse BPD psychopathology. Our results confirm the role of ACEs in contributing to social cognition impairments in BPD and related symptomatology from a neurobiological perspective.

Corticolimbic Connectivity Mediates the Relationship between Adverse Childhood Experiences and Symptom Severity in Borderline Personality Disorder.

Hormonal disorders are a source of cerebellar ataxia in both children and adults. Normal development of the cerebellum is critically dependent on thyroid hormone, which crosses both the blood–brain barrier and the blood–cerebrospinal fluid barrier thanks to specific transporters, including monocarboxylate transporter 8 and the organic anion-transporting polypeptide 1C1. In particular, growth and dendritic arborization of Purkinje neurons, synaptogenesis, and myelination are dependent on thyroid hormone. Disturbances of thyroid hormone may also impact on cerebellar ataxias of other origin, decompensating or aggravating the pre-existing ataxia manifesting with motor ataxia, oculomotor ataxia, and/or Schmahmann syndrome. Parathyroid disorders are associated with a genuine cerebellar syndrome, but symptoms may be subtle. The main conditions combining diabetes and cerebellar ataxia are Friedreich ataxia, ataxia associated with anti-GAD antibodies, autoimmune polyglandular syndromes, aceruloplasminemia, and cerebellar ataxia associated with hypogonadism (especially Holmes ataxia/Boucher–Neuhauser syndrome). The general workup of cerebellar disorders should include the evaluation of hormonal status, including thyroid-stimulating hormone and free thyroxine levels, and hormonal replacement should be considered depending on the laboratory results. Cerebellar deficits may be reversible in some cases.

Endocrine disorders and the cerebellum: from neurodevelopmental injury to late-onset ataxia.

Background The prevalence of female alcohol and substance abusers has markedly increased. The main objective of this research was to explore personality profiles among females who had alcohol and opiate dependence. Aim The aim of the study is to analyse if there is differences in personality profiles of females addicted to alcohol and opiates. We hypothesized that there might be significant differences in personality profiles among subgroups of women who present with alcohol and opiate use disorders. Subjects and methods Of 157 consecutive women with diagnosis of alcohol/opiate addiction, 62 fulfilled following inclusion criteria: age 19-45 years, abstinence from alcohol and opiates for at least 10 days prior to enrollment. Alcohol-dependent group consisted of 30 females, while opiate-dependent group consisted of 32 females. The control group involved 30 age-matched randomly chosen healthy women. The data were collected using the Revised NEO Personality Inventory (NEO-PI-R). The multiple stepwise discriminant analysis was used to determine relations between personality traits and the probability of belonging to one of the study groups. Results Significant differences in the NEO-PI-R scores were observed between groups for all main personality traits except for Openness to Experience. Compared with controls, substance-dependent women scored significantly higher on Neuroticism and lower on Conscientiousness. Opiate-dependent females scored the highest on Neuroticism and on Extraversion and lowest on Agreeableness and on Conscientiousness. Alcohol-dependent females scored higher on Conscientiousness and lower on Neuroticism compared to opiate-dependent women. Conclusions The results of our study confirmed significant characteristics in personality profiles among females with alcohol and opiate dependence, as well as the difference between these two groups of substance abusers and their healthy controls. The distinct personality characteristics among different groups of substance addicted women should be taken into account when creating the most effective program of prevention and therapeutic approaches in this specific cohort.

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Five-Factor Model Personality Profiles: The Differences between Alcohol and Opiate Addiction among Females.

An increasing number of findings confirm the significance of cerebellum in affecting regulation and early learning Most consistent findings refer to association of congenital vermis anomalies with deficits in nonmotor functions of cerebellum In this paper we presented a young woman who was treated since sixteen years of age for polysubstance abuse, affective instability, and self-harming who was later diagnosed with borderline personality disorder Since the neurological and neuropsychological reports pointed to signs of cerebellar dysfunction and dysexecutive syndrome, we performed magnetic resonance imaging of brain which demonstrated partially developed vermis and rhombencephalosynapsis These findings match the description of cerebellar cognitive affective syndrome and show an overlap with clinical manifestations of borderline personality disorder

https://downloads.hindawi.com/journals/crim/2014/894263.pdf

Snezana M Svetozarevic

Papers

Five-Factor Model Personality Profiles: The Differences between Alcohol and Opiate Addiction among Females.

Cerebellar cognitive affective syndrome presented as severe borderline personality disorder.