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 elusive. The current paper reviews all genome-wide association studies conducted in the past ten years, sampling patients with AUD and co-occurring mood or anxiety disorder(s). (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 the total variance, larger samples consisting of multiple refined comorbid combinations and confirmed by re-sequencing approaches will be necessary to disentangle the genetic architecture of dual diagnosis.

Based on the limited research focusing on the severity of cognitive deterioration in schizophrenia with preceding toxoplasmosis, we sampled 89 demographically matched paranoid schizophrenia patients (mean age 38.97 years) with (n = 42) and without (n = 47) seroprevalence of IgG type anti T. gondii antibodies as marker of past infection. They underwent examination of verbal memory (10 words Luria test), logical memory and visual memory (BVRT), processing speed (TMT-A/DSST) and executive functions (TMT-B/verbal fluency). We compared the results of both groups, taking into account the normative values for the Bulgarian population where available. We also compared the two groups in terms of clinical severity as evidenced by positive, negative and disorganization sub-scores of the PANSS. While both groups were expectedly under the population norms for verbal and logical memory, seropositive patients showed significantly bigger impairment in verbal memory (Luria Smax = 72.85 vs 78.51; p = 0.029), psychomotor speed (TMT-A 50.98 s vs 44.64 s; p = 0.017), semantic verbal fluency (27.12 vs 30.02; p = 0.011) and literal verbal fluency (17.17 vs 18.78; p = 0.014) compared to the seronegative ones. In addition to that, they gave less correct answers on the BVRT (2.98 vs 4.09; p = 0.006) while making markedly more errors (13.95 vs 10.21; p = 0.002). Despite not reaching statistical significance, past toxoplasmosis was associated with higher score on the PANSS disorganization sub-scale (16.50 points vs 14.72 points) and with lower educational attainment. Our results suggest a more profound neuropathological insult(s) resulting in greater cognitive impairment in schizophrenia cases that are exposed to T. gondii infection.

CYP2D6 and CYP2C19 are enzymes of essential significance for the pharmacokinetics of a multitude of commonly used antidepressants, antipsychotics, antiemetics, β-blockers, opioids, antiestrogen, antacids, etc. Polymorphisms in the respective genes are well established as resulting in functional differences, which in turn can impact safety and efficacy. Importantly, the prevalence of genetic CYP2D6 and CYP2C19 variability differs drastically between populations. Drawing on the limited information concerning genotype frequencies in Bulgaria, we here analyzed 742 Bulgarian psychiatric patients predominantly diagnosed with depression and/or anxiety. Specifically, we analyzed frequencies of CYPC19*2, *4 and *17, as well as of CYP2D6*2, *3, *4, *5, *6, *10 and *41. In total, 571 out of 742 patients (77%) carried at least one variant which impacts metabolizer status. Overall, 48.6% of the studied individuals were classified as non-normal metabolizers of CYP2D6 with most exhibiting reduced function (38.2% intermediate metabolizers and 6.6% poor metabolizers). In contrast, for CYP2C19, the majority of non-normal metabolizers showed increased functionality (28.9% rapid and 5.5% ultrarapid metabolizers), while reduced activity metabolizer status accounted for 25.6% (23.8% intermediate and 1.8% poor metabolizers). These results provide an important resource to assess the genetically encoded functional variability of CYP2D6 and CYP2C19 which may have significant implications for precision medicine in Bulgarian psychiatry practice.

Introduction: Stigmatising attitudes towards mentally ill people are present among healthcare professionals. The aim of the study was to evaluate medical students' attitudes in five medical schools from Albania, Bulgaria, Moldova, Romania and Serbia and to determine if psychiatry clerkship improves these attitudes. Methods: In the first stage, the study included students from the first and final years of medical school; in the second stage, only final-year students were included; The Mental Illness Clinicians' Attitude Scale (MICA-2) and the Attribution Questionnaire (AQ-9) were used in this study. The total sample comprised 1,526 medical students in the first stage and 614 in the second stage. Results: The analysis of the average AQ-9 and MICA-2 scores between countries revealed significant differences (p<0.05). Multivariable analysis showed that female students were 30% more likely to have elevated AQ-9 scores than male students (p=0.029). Final-year students had a significantly lower chance of having a higher MICA-2 score compared to first-year students (OR=0.7; p<0.05). Conclusions: Psychiatry clerkship contributes to a decrease in the level of stigmatising attitudes among medical students. Further research is required to assess the curricula to achieve better results in reducing stigma among future doctors.

The study aimed to assess the impact of clinical symptoms and cognitive impairment on disability in patients with paranoid schizophrenia (PS). Methods: 108 patients with schizophrenia were included (66 male and 42 female). Their average age was 38.86 ± 10.02 years and the disease duration was 12.80 ± 8.20 years, with mean disease onset of 24 years. Clinical symptoms were assessed with the PANSS, and cognitive performance was measured using a seven-item neurocognitive battery. The disability level of the subjects was assessed using the World Health Organization—Disability Assessment Schedule 2.0 (WHO-DAS 2.0). The relation between the variables studied was assessed using Spearman’s rank correlation coefficient (r_s) at a probability level of p < 0.05. Results: An increase in symptom severity resulted in worsening of the “participation in society” (r = 0.56, p < 0.01), “life activities—household” (r = 0.55, p < 0.01), and “getting along with people” (r = 0.59, p < 0.01) WHO-DAS 2.0 domains. Positive symptoms (13.89 ± 3.48) correlated strongly with “getting along with people” (r = 0.55, p < 0.01), “life activities—household” (r = 0.58, p < 0.01), and “participation in society” (r = 0.62, p < 0.01), and negative symptoms (14.25 ± 4.16) with “participation in society” (r = 0.53, p < 0.01) and “life activities—household” (r = 0.48, p < 0.01). Symptoms of disorganization (15.67 ± 4.16) had the highest impact on “life activities—household” (r = 0.81, p < 0.01), “getting along with people” (r = 0.56, p < 0.05), and “participation in society” (r = 0.65, p < 0.01). Episodic memory (r = −0.28, p < 0.01) was remotely related to comprehension and communication. The information processing speed (r_s = 0.38, p < 0.01), visual memory (r_s = −0.30, p < 0.01), and focused executive functions showed moderate correlations with all domains on the WHO-DAS 2.0 scale (r_s = 0.38, p < 0.01). Attention (r_s = −0.33, p < 0.01) was moderately related to community activities. Semantic (r_s = −0.29, p < 0.01) and literal (r_s = −0.27, p < 0.01) verbal fluency demonstrated weak correlations with “cognition—understanding”, “getting along with people”, and “participation in society”. Conclusion: Symptoms of disorganization and disturbed executive functions contribute most to disability in patients with schizophrenia through impairment of real-world functioning, especially in social interactions and communication. Severe clinical symptoms (negative and disorganization-related ones) as well as deficits in executive function, verbal memory, and verbal fluency cause the biggest problems in the functional domains of interaction with other people and participation in society.