Search

Introduction: Irritable mood (IM) and subthreshold hypomanic symptoms are reported in half and two-fifths of major depressed subjects respectively, but their clinical and prognostic meanings remain unclear. The aim of this study was to test the clinical usefulness of 2 specifiers in DSM-IV major depressive disorder (MDD): IM occurring during an index episode (IM+) and lifetime episodes of elated mood or IM with at least 2 concurrent hypomanic symptoms (subthreshold hypomanic episodes [SHEs])., Method: We included 482 outpatients with MDD participating in the Combining Medications to Enhance Depression Outcome study (mean age 43.14 ± 12.46 years, 144 males - 30%). The main aim of the original study was to test whether 2 different medications when given in combination as the first treatment step, compared to 1 medication, would improve antidepressant response., Results: IM + subjects (N = 349; 70%) were younger and more often females, with a more severe depression, a more marked social impairment, and more psychiatric comorbidities. The IM + group was also characterized by higher levels of suicidal ideation and more cases of emotional abuse. The combination of IM+ and SHEs was associated with an even more severe clinical picture. Limitations include the post hoc method, incomplete assessment of bipolar validators (e.g., family history of bipolar illness), personality disorders and suicide attempts., Conclusions: The presence of IM and SHEs in MDD correlate with an overall more severe clinical condition., (© 2021 S. Karger AG, Basel.)

Background: The genetic background of the antidepressant response to pharmacological treatment in bipolar disorder (BD) remains elusive. This issue is of primary relevance in that the depressive phases of BD are difficult to treat and they are associated with suicide., Aim: We investigated the role of a set of genetic variations (single-nucleotide polymorphisms) harbored by matrix metalloproteinases (MMPs) as predictors of response to treatment in depressed BD patients., Methods: 654 BD patients from the publicly available Systematic Treatment Enhancement Program for Bipolar Disorder study were investigated. The outcome was the number of depressive events corrected by the number of times patients were assessed. Clinical and sociodemographic variables were tested as possible stratification factors and included in the analysis if necessary. Genetic predictors were 43 SNPs harbored by 17 MMPs. Imputation, quality check and pruning were conducted according to standards. RESULTS were corrected for multitesting., Results: rs486055 (MMP-10) was associated with the outcome. TT homozygotes had 5.08 ± 3.51 events, CT had 3.47 ± 3.18 and CC had 2.57 ± 2.96 depressive events corrected for the times they had been assessed. The time during which BD patients were observed was not significantly different between the rs486055 genotypes. We found evidence that MMP-10 may be a mediator of the number of depressive phases during BD. Due to the limits of the study including the small-to-medium sample size, the naturalistic design and the possible occurrence of false-positive findings, independent analyses are warranted.

Background: Serotonergic genes have been widely investigated regarding antidepressant response in major depressive disorder (MDD) but results are still not univocal., Methods: 159 MDD patients treated with citalopram were genotyped and evaluated by the 21-item Hamilton Depression Rating Scale at the beginning and every 4 weeks during the 12-week follow-up. Four serotonin-related genetic variants were tested for association with treatment outcome: tryptophane hydroxylase 1 (TPH1) rs1800532, monoamine oxidase A µVNTR, serotonin 2A receptor rs6311 and serotonin 2C receptor rs6318. The effect of these polymorphisms was tested both in the whole sample and in depressive subtypes with usually higher clinical severity: psychotic and melancholic MDD., Results: No effect on response, remission and symptom improvement was found for the four polymorphisms. However, rs1800532 was found to affect the outcome depending on the MDD subtype: the A allele predicted worse response both in MDD with psychotic (F₆,₃₇₈ = 2.90; p = 0.009) and melancholic (F₆,₃₈₁ = 2.86; p = 0.0097) features., Conclusions: The A allele at TPH1 rs1800532 may be associated with citalopram efficacy only in melancholic and psychotic MDD. These results suggest the usefulness of investigating the effect of genetic variants in conjunction with specific clinical features., (Copyright © 2012 S. Karger AG, Basel.)

In the present study, we aimed to confirm the previous finding of an association between GRIK4 and GNB3 variants (rs195478 and rs5443) and remission and treatment resistance in major depression, using a multicenter sample of 223 patients. We did not find any supporting evidence for such associations. These conflicting data may result from difficulties in the replication of candidate gene association studies., (Copyright © 2012 S. Karger AG, Basel.)

Aim: The present study aimed to explore whether some single nucleotide polymorphisms (SNPs) within the BDNF gene could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia, and whether they could predict clinical outcomes in Korean inpatients treated with antidepressants, mood stabilizers and antipsychotics, respectively., Methods: One hundred and forty-five patients with MD, 132 patients with BD, 221 patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for 5 BDNF SNPs (rs2030324, rs7103873, rs10835210, rs11030101 and rs6265). Baseline and final clinical measures--including the Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Positive and Negative Symptoms Scale for patients with MD, BD and schizophrenia, respectively--were recorded., Results: rs10835210 CA and rs11030101 AT genotype frequencies were higher in BD and schizophrenia patients than in healthy and MD subjects. No significant association was found with clinical improvement., Discussion: Our findings provide evidence of an association between BDNF and BD and schizophrenia. However, taking into account the several limitations of our study, including the moderately small sample size, further research is needed to draw more definitive conclusions., (Copyright © 2011 S. Karger AG, Basel.)

Suicide, one of the leading causes of death among young adults, seems to be plausibly modulated by both genetic and personality factors. The aim of this study was to dissect the potential association between genetics and temperament in a sample of 111 suicide attempters and 289 healthy controls. We focused on 4 genes previously investigated in association with suicide on the same sample: the nitric oxide synthase 1 and 3 (NOS1 and NOS3), the neuronal cell adhesion molecule 1 (NCAM1), and the tachykinin receptor 1 (TACR1) genes. In particular, we investigated whether a set of genetic variants in these genes (NOS1: rs2682826, rs1353939, rs693534; NOS3: rs2070744, rs1799983, rs891512; NCAM1: rs2301228, rs1884, rs1245113, rs1369816, rs2196456, rs584427; TACR1: rs3771810, rs3771825, rs726506, rs1477157) were associated with temperamental traits at the Temperament and Character Inventory (TCI). No strong evidence was found for the association between TCI personality traits and the polymorphisms considered in the 4 genes, with the exception of an association between reward dependence trait and the rs2682826 SNP in NOS1 in the healthy sample. However, this result could be plausibly interpreted as a false-positive finding. In conclusion, our study did not support the thesis of a direct modulation of these genes on temperament; however, further studies on larger samples are clearly required in order to confirm our preliminary findings and to exclude any possible minor influence., (Copyright © 2011 S. Karger AG, Basel.)

Aim: The aim of the present review is to summarize available evidence about the efficacy and side effects of novel antidepressants for the treatment of panic disorder., Methods: A literature search was undertaken using MEDLINE, ISI web of knowledge and references of retrieved articles. The search included articles published in English up to September 2009. Both controlled and uncontrolled trials were included. The quality of the reviewed articles was also assessed., Results: Fourteen mainly poor-quality studies were included. Mirtazapine showed some efficacy in reducing the number and the severity of panic symptoms in many uncontrolled studies and was comparable to selective serotonin reputake inhibitors (SSRIs) in direct-comparison studies. Reboxetine was significantly more efficacious than placebo but less effective than SSRIs. Further uncontrolled studies suggested preliminary evidence for the use of milnacipran and duloxetine as well. All drugs were usually well tolerated., Discussion: Current studies do not yet provide convincing evidence supporting the efficacy of mirtazapine, reboxetine, milnacipran and duloxetine for the treatment of panic disorder patients. However, on account of positive preliminary results, further research is warranted., (Copyright © 2010 S. Karger AG, Basel.)

Personality influences several characteristics of normal and pathologic behaviors and it is associated with neurotransmitter systems that are under genetic control. The dopaminergic system has been proposed to play a role in the modulation of personality traits. In the present study, variants of the tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC) genes (for TH: rs3842727, rs6356; for DDC: rs1451371, rs1470750, rs998850) were investigated in 111 suicide attempters and 289 healthy subjects to assess the involvement of the dopaminergic synthesis pathway in personality traits. No strong evidence was found for the associations between personality and TH or DDC in overall tests. An interaction effect of genotype and diagnosis was present, with TH and DDC SNPs having a greater effect on the respective personality dimensions in the group of suicide attempters. Because of the risk of false positives, these findings should be interpreted with highest caution. Direct replication attempts within independent groups of suicide attempters will help to resolve this question., (Copyright 2009 S. Karger AG, Basel.)

We previously investigated a group of single-nucleotide polymorphisms of a set of genes coding for heat shock proteins (HSPA1A, HSPA1B and HSPA1L) and found a significant association between one HSPA1B variation and schizophrenia (SZ). We now report an association between a set of variations (rs2227956, rs2075799, rs1043618, rs562047 and rs539689) within the same genes and a larger sample of schizophrenic inpatients. A single variation, rs539689 (HSPA1B), was found to be marginally associated with Positive and Negative Syndrome Scale (PANSS) positive scores at discharge, and haplotype analysis revealed a significant association between improvement in PANSS scores with both A-C-G-G and A-C-G-G haplotypes. These findings further support a role of heat shock proteins in the pathophysiology of SZ., (Copyright 2009 S. Karger AG, Basel.)

Background: According to the self-medication hypothesis, individuals with depression and anxiety disorders use alcohol to control their symptoms and subsequently become dependent. Conversely, alcohol dependence disorder (ADD) can cause or exacerbate psychiatric disorders. This study analyzed the characteristics of depression and social phobia secondary to ADD. (1) What is their functional impact? (2) Are they independent or associated conditions? (3) Do they completely remit in abstinent individuals? (4) Is the remission of one disorder associated with the remission of the other disorder?, Methods: Sixty-four inpatients with ADD were evaluated with depression and anxiety disorder scales upon admission to hospital and after 5 weeks of detoxification., Results: Baseline comparisons differentiated patients with a Hamilton Rating Scale for Depression (HDRS) score > 35 (n = 50; 78%) from those with an HDRS score < or = 35 by higher levels of generalized anxiety and lower global functioning. Patients with generalized social phobia [Leibowitz Social Anxiety Scale (LSAS) score > 60: n = 20; 31.2%] were not distinguishable from those with an LSAS score < or = 60 by depressive and anxiety disorder symptoms. In postdetoxification assessment, patients who remitted from depression (HDRS score < 7: n = 35; 54.6%) had a lower generalized anxiety and marginally higher levels of hypochondriasis compared to nonremitter subjects (HDRS score > or = 7). Patients who remitted from social phobia (LSAS score < 30: n = 32; 50%) did not significantly differ from nonremitter subjects in depressive and anxiety disorder symptoms. Generalized anxiety (Hamilton Rating Scale for Anxiety) and hypochondriasis (Whiteley Index) were the significant predictors of global functioning (Global Assessment Scale)., Conclusions: Depression and social phobia secondary to ADD are independent conditions that do not completely remit after cessation of drinking. Specific treatments are needed to reduce residual depressive and anxiety symptoms in abstinent alcoholics., (2008 S. Karger AG, Basel)

Background: This study aims to detect the impact of stroke on the occurrence of dementia and cognitive impairment/no dementia (CIND) in different age, sex, and education groups., Methods: Persons with dementia (DSM-III-R) or CIND were identified by a two-phase study design among 7,930 persons from the population-based Faenza Community Aging Study., Results: Subjects with a history of stroke had increased risk of both dementia [risk ratio (RR) = 3.7; 95% confidence interval (CI) = 3.1-4.4] and CIND (RR = 1.7, 95% CI = 1.4-2.2). These associations were stronger in the younger-old (61-74 years) than in the older-old (75+ years), and among higher-educated (4+ years) than lower-educated (0-3 years of schooling) persons. Dementia and CIND prevalence among stroke subjects was similar to the prevalence detected among subjects 10 years older but without a history of stroke. In stroke subjects, dementia prevalence became higher than CIND prevalence 10 years earlier than in non-stroke subjects. A combined effect for dementia due to a history of stroke, increasing age, and decreasing years of schooling was detected., Conclusions: Stroke is a strong risk factor for dementia among younger-old and higher-educated subjects; in the presence of a stroke, dementia onset might occur about 10 years earlier, possibly by accelerating the progression from CIND to dementia.

Objective: To evaluate the age, gender and education distribution of both cognitive impairment and dementia in the whole old age range of the elderly (from 61 years of age and over)., Subjects and Methods: The study population consisted of all subjects born in 1930 or before, living in the municipality of Faenza and Granarolo, Italy (n = 7,930). A two-phase study design was implemented, by using the Mini-Mental State Examination and Global Deterioration Scale as screening instruments. The DSM-III-R diagnostic criteria were used for the clinical diagnosis of dementia. A subject was classified as affected by cognitive impairment, no dementia (CIND) if he/she scored 2 or more standard deviations lower than the corrected mean MMSE score., Results: The prevalences of dementia and CIND were 6.5 per 100 (95% CI 5.9-7.0) and 5.1 per 100 (95% CI 4.6-5.6), respectively. The prevalence of CIND was higher than that of dementia in the youngest old groups (61-74 years), both in men and women, whereas the opposite pattern was present among the older old (75+). In the older age groups, dementia prevalence increased exponentially with age, while CIND prevalence was more stable. There was not a substantial gender difference in CIND prevalence in all ages. Only in the subpopulation of higher educated subjects, women had a higher prevalence of both dementia and CIND than men. Lower educated subjects had a higher prevalence of both dementia and CIND. When compared to higher educated persons, subjects without any schooling had odds ratios of 10.9 (CI 7.0-16.7) and 16.7 (CI 11.2-25.0) for dementia and CIND, respectively., Conclusions: Cognitive impairment is very common in the younger old ages (under 70 years of age), whereas dementia becomes predominant after 75 years of age. Both conditions are strongly related to the educational level.

Background: Underrecognition and undertreatment of depression in primary care has been regarded as a major public health problem. In contrast, some studies found that among patients labeled as depressed by primary-care physicians (PCPs), a relevant proportion do not satisfy international diagnostic criteria for depression. The aims of this study are: (1) to assess disparity between PCP diagnosis and research diagnosis of depression; (2) to compare antidepressant treatment in concordant and discordant cases of depression., Methods: Data are gathered from a national survey on depressive disorders in primary care, conducted with the collaboration of 191 PCPs. Three hundred and sixty-one PCP patients were evaluated, and their psychiatric diagnosis was established by the 'unaided' PCPs and by using a research interview for depression., Results: PCPs recognized 79.4% of cases of depression and prescribed antidepressants to 40.9% of them. Yet, 45.0% of patients labeled as depressed by the PCPs were not cases of depression according to ICD-10 criteria; 26.9% of false-positive cases received an antidepressant. Globally, 35% of antidepressants for 'depression' were prescribed to false-positive cases., Conclusions: Underrecognition and undertreatment of depression in primary care seem to be less alarming. Conversely, PCP diagnoses of depression appear to be more inclusive than psychiatric diagnostic criteria. A possible consequence of this apparently more inclusive diagnostic threshold may be an excessive use of antidepressants. These changes require a corresponding change in research, toward efficacy and safety of the treatment of milder cases, and in education, toward the distinction between the management of mild and severe cases of depression., (Copyright (c) 2005 S. Karger AG, Basel.)

Literature data consistently show different prevalence estimates of dementia when different classification systems are used in the same population. Very few data are available for the oldest old of the elderly. We investigated the occurrence of dementia among 34 nonagenarians and centenarians according to four classification systems: the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, third edition revised (DSM-III-R) and fourth edition (DSM-IV), the World Health Organization's International Classification of Diseases, 10th revision (ICD-10), and the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). Cognitive functioning, work, social function and independence in activities of daily living were evaluated by using an extensive neuropsychological examination. The prevalence (95% CI) of dementia was the following: 47.1% (95% CI 30.3-63.8) with the DSM-III-R criteria, 41.2% (95% CI 24.6-57.7) with the DSM-IV criteria, 29.4% (95% CI 14.1-44.7) with the ICD-10 criteria and 38.2% (95% CI 21.9-54.6) with the CAMDEX. The factors that best predicted disagreement between DSM-III-R and DSM-IV were calculation impairment and the presence or absence of personality changes. DSM-III-R and ICD-10 were differentiated by the weight given to executive functions that all have to be impaired according to ICD-10, whereas progressive deterioration differentiated CAMDEX from DSM-III-R. It should be noted that although the DSM-III-R diagnoses differ by a factor of 1.6 times from the ICD-10 and 1.2 times from the CAMDEX diagnoses, we are speaking about dementia, which is very frequent in nonagenarians and centenarians. Moreover, with regard to public health, an estimation of the number of subjects who will lose their autonomy is rather more useful and informative than simple prevalence figures of dementia by itself. In this light, classification systems, such as the ICD-10, that do not include impairment of social function as a criterion for assessing dementia become less adequate., (Copyright 2004 S. Karger AG, Basel)

Background: Although many significant studies of late luteal phase dysphoric disorder (LLPD) have been carried out, some conflicting findings on the relationships between personality disorders, depressive symptoms, hostility and LLPD deserve further investigation., Methods: Forty-three LLPD patients and 85 control subjects, evaluated by prospective daily ratings during two symptomatic cycles, received a detailed psychiatric evaluation, including the sections for psychotic, affective and anxiety disorders of the Structured Clinical Interview for DSM-III-R nonpatient version and the section for personality disorders; the Buss Durkee Inventory for Assessing Different Kinds of Hostility and the Montgomery-Asberg Depression Rating Scale., Results: The odds of suffering from LLPD are about nine-fold (crude odds ratio, OR = 9.23, 95% confidence interval, CI 3.98-21.39) among women with mild or moderate depressive symptoms. When two age strata (below and above 30) are analyzed separately, the association between LLPD and depressive symptoms is strong and positive in both strata, while the association between LLPD and avoidant personality disorder is found only among older women (adjusted OR = 8.26, p < 0.05, 95% CI 1.03-66.35)., Conclusions: The major finding from this preliminary study is the association between LLPD and depressive symptoms. Conversely, the association between LLPD and avoidant personality disorder remains controversial and seems to be dependent on age. Our findings support the hypothesis that LLPD and avoidant personality disorder may be considered as part of the spectrum of recurrent mood disorder rather than as qualitatively distinct nosological entities. Future studies are needed, adopting prospective, longitudinal assessments of personality prior to the onset of LLPD., (Copyright 2000 S. Karger AG, Basel.)