Introduction: More than half of psychiatric patients have comorbid substance use disorder (dual diagnosis) and this rate, confirmed by many epidemiological studies, is substantially higher compared to general population. Combined operation of self-medication mechanisms, common etiological factors, and mutually causative influences most likely accounts for comorbidity, which, despite its clinical prevalence, remains underrepresented in psychiatric research, especially in terms of neuroimaging. The current paper attempts to review and discuss all existing methodologically sustainable structural and functional neuroimaging studies in comorbid subjects published in the last 20 years. Methods: Performing a systematic PubMed/MEDLINE, Web of Science, and Cochrane databases search with predefined key-words and selection criteria, 43 structural and functional neuroimaging studies were analyzed. Results: Although markedly inconsistent and confounded by a variety of sources, available data suggest that structural brain changes are slightly more pronounced, yet not qualitatively different in comorbid patients compared to non-comorbid ones. In schizophrenia (SZ) patients, somewhat greater gray matter reduction is seen in cingulate cortex, dorsolateral prefrontal and frontotemporal cortex, limbic structures (hippocampus), and basal ganglia (striatum). The magnitude of structural changes is positively correlated to duration and severity of substance use, but it is important to note that at least in the beginning of the disease, dual diagnosis subjects tend to show less brain abnormalities and better cognitive functioning than pure SZ ones suggesting lower preexisting neuropathological burden. When analysing neuroimaging findings in SZ and bipolar disorder subjects, dorsolateral prefrontal, cingular, and insular cortex emerge as common affected areas in both groups which might indicate a shared endophenotypic (i.e., transdiagnostic) disruption of brain networks involved in executive functioning, emotional processing, and social cognition, rendering affected individuals susceptible to both mental disorder and substance misuse. In patients with anxiety disorders and substance misuse, a common neuroimaging finding is reduced volume of limbic structures (n. accumbens, hippocampus and amygdala). Whether this is a neuropathological marker of common predisposition to specific behavioral symptoms and drug addiction or a result from neuroadaptation changes secondary to substance misuse is unknown. Future neuroimaging studies with larger samples, longitudinal design, and genetic subtyping are warranted to enhance current knowledge on comorbidity.
(1) Background: Comorbidity between Alcohol Use Disorders (AUD), mood, and anxiety disorders represents a significant health burden, yet its neurobiological underpinnings are still elusive. The current paper reviews all genome-wide association studies conducted in the past ten years, sampling those on AUD and mood or anxiety disorders. (2) Methods: In keeping with PRISMA guidelines, we searched EMBASE, Medline/PUBMED, and PsycINFO databases (January 2010 to December 2020), including references of enrolled studies. Study selection was based on predefined criteria and data underwent a multistep revision process. (3) Results: 15 studies were included. Some of them explored dual diagnoses phenotypes directly while others employed correlational analysis based on polygenic risk score approach. Their results support the significant overlap of genetic factors involved in AUDs and mood and anxiety disorders. Comorbidity risk seems to be conveyed by genes engaged in neuronal development, connectivity, and signaling although the precise neuronal pathways and mechanisms remain unclear. (4) Conclusion: given that genes associated with complex traits including comorbid clinical presentations are of small effect, and individually responsible for a very low proportion of total variance, larger samples consisting of multiple refined comorbid combinations confirmed by re-sequencing approaches will be necessary to disentangle the genetic architecture of dual diagnosis.
Dementia comprises several neurodegenerative disorders with similar neuropsychiatric features and Alzheimer's disease (AD) is the most common of them. Genetic factors are strongly implicated into its etiology especially for early-onset cases (EOAD) occuring before the age of 65. About 10% of these are inherited in autosomal dominant fashion via pathogenic polymorphisms in three genes-APP, PSEN-1, and PSEN-2. Despite genotypic clarity, however, phenotypic variability exists with different symptom constellations observed in patients with identical mutations. Below, we present a case of a 39-year-old male with a family history for early onset dementia who was referred to our department with anamnesis for abrupt behavioral change 7 months prior to hospitalization-noticeable slowing of speech and reactivity, impaired occupational functioning and irritability, followed by aphasic symptoms and transient episodes of disorientation. He was followed up for 2 years and manifested rapidly progressing cognitive decline with further deterioration of speech, apraxia, acalculia, ataxia, and subsequently bradykinesia and tremor. Based on the clinical and neuroimaging findings (severe cortical atrophy), familial EOAD was suspected and a whole exome sequence (WES) analysis was performed. It identified a heterozygous missense variant Leu424Val (g.71074C > G) in PSEN-1 gene considered to be pathogenic, and only reported once until now in a Spanish patient in 2009. Despite genotype identity however, distinct phenotypic presentations were observed in the two affected subjects, with different neuroimaging findings, and the presence and absence of seizures in the Spanish and Bulgarian case, respectively. Besides, myoclonus and spastic paraparesis considered "typical" EOAD clinical features were absent. Age of symptom onset was consistent with two of the reported mutations affecting 424 codon of PSEN-1 gene and significantly earlier than the other two implying that factors influencing activity of PSEN-1 pathological forms are yet to be clarified. Furthermore, our patient had co-occurring lupus erythematosus (LE) and we suggest that this condition might be etiologically linked to the PSEN-1 mutation. In addition to illustrating the symptomatic heterogeneity of PSEN-1 caused EOAD, our study confirms that in patients presenting Frontiers in Psychiatry | www.frontiersin.org
Introduction: Suicide is a major public health problem but factors determining suicide risk are still unclear. Studies in this field in Bulgaria are limited, especially on a regional level.Methods: By a cross-sectional design, we accessed the medical records of all psychiatric patients committed suicide over a 10-year period (2009–2018) in one major administrative region of Bulgaria. A statistical analysis was performed of the association between age of suicide as an indirect yet measurable expression of the underlying suicidal diathesis and a number of socio-demographic and clinical characteristics.Results: Seventy-seven of 281 suicides (28%) had psychiatric records. Most common diagnoses were mood disorders (44%), followed by schizophrenia (27%), anxiety disorders (10%), substance use disorders (9%) and organic conditions (8%). Male gender, single/divorced marital status, early illness onset, co-occurring substance misuse and lower educational attainment (for patients aged below 70) were significantly associated with earlier age of suicide whereas past suicide attempts and psychiatric hospitalizations, comorbid somatic conditions and unemployment showed insignificant association. Substantial proportion of patients (60%) had contacted psychiatric service in the year preceding suicide, with nearly half of these encounters being within 30 days of the accident.Conclusion: Severe mental disorders are major suicide risk factor with additional contribution of certain socio-demographic and illness-related characteristics. Monitoring for suicidality must be constant in chronic psychiatric patients. Registration of suicide cases in Bulgaria needs improvement in terms of information concerning mental health. More studies with larger samples and longitudinal design are needed to further elucidate distal and proximal suicide risk factors.
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