Konstantinos Papageorgiou

Emotion Recognition in Individuals at Clinical High-Risk for Schizophrenia

Problems in the perception of emotional material, in particular deficits in the recognition of negative stimuli, have been demonstrated in schizophrenia including in first-episode samples. However, it is largely unknown if emotion recognition impairment is present in people with subthreshold psychotic symptoms. Here, we examined the capacity to recognize facially expressed emotion and affective prosody in 79 individuals at ultra high-risk for psychosis, 30 clinically stable individuals with first-episode schizophrenia assessed as outpatients during the early recovery phase of illness, and 30 unaffected healthy control subjects. We compared (1) scores for a combined fear-sadness aggregate index across face and voice modalities, (2) summary scores of specific emotions across modalities, and (3) scores for specific emotions for each sensory modality. Findings supported deficits in recognition of fear and sadness across both modalities for the clinical groups (the ultra high-risk and first-episode group) as compared with the healthy controls. Furthermore, planned contrasts indicated that compared with the healthy control subjects, both clinical groups had a significant deficit for fear and sadness recognition in faces and for anger recognition in voices. Specific impairments in emotion recognition may be apparent in people at clinical high-risk for schizophrenia before the full expression of psychotic illness. The results suggest a trait deficit and an involvement of the amygdala in the pathology of ultra high-risk states.

The Community Assessment of Psychic Experience (CAPE) questionnaire as a screening-instrument in the detection of individuals at ultra-high risk for psychosis ☆

Recent findings on intervention options in individuals at ultra-high risk (UHR) for psychosis underline the necessity of a screening tool that facilitates early detection in low-threshold, non-specialized settings. The aim of this study was to examine, whether the Community Assessment of Psychic Experience (CAPE) could be used as a screening tool to detect individuals at an increased risk for developing psychosis in a clinical, help-seeking population. The utility of the CAPE was assessed against the Comprehensive Assessment of At-Risk Mental States (CAARMS). The CAPE is a 42-item self-report questionnaire that proved to be stable, reliable and valid for self reported psychotic-like experiences in the general population. 165 individuals between 13 and 24years of age were assessed for being at UHR for developing psychosis. 50.9% individuals were CAARMS-positive and 49.1% were CAARMS-negative. The ROC-analysis provided two cut-off points: The cut-off value of 3.20 in the positive dimension showed a sensitivity of 67%, a specificity of 73%, a positive predictive value of 72% and a negative predictive value of 68%. The cut-off value of 2.80 in the positive dimension showed a higher sensitivity (83%) and a better negative predictive value (74%), but a lower specificity (49%) and a reduced positive predictive value (63%). Our results show promise that the CAPE is a valid, simple and cost-effective instrument for detecting individuals at UHR in a clinical population. It may represent a useful screening tool for calling clinicians attention to subjects with psychotic-like experiences.

The impact of COMT gene polymorphisms on suicidality in treatment resistant major depressive disorder--a European multicenter study.

Many association studies have reported associations between the catechol-O-methyltransferase (COMT) gene and psychiatric disorders including major depression (MDD). The COMT gene has further been associated with suicidal behaviour, as well as with treatment response, although with conflicting results. In the present study, we further elucidate the impact of COMT in treatment response in MDD patients with suicide risk and/or a personal history of suicide attempts. Two hundred fifty MDD patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for seven SNPs (rs4680, rs2075507, rs737865, rs6269, rs4633, rs4818 and rs165599) within the COMT gene. With regard to suicide risk and personal history of suicide attempts, neither single marker nor haplotypic association was found with any SNP after multiple testing correction. In non-responders, we found significant single marker and haplotypic association with suicide risk, but not in responders. The same holds true for both remitters and non-remitters, and when testing for association with a personal history of suicide attempts and treatment response phenotypes. In conclusion, we found significant association of COMT SNPs with suicide risk in MDD patients not responding to antidepressant treatment. Larger well-defined cohorts will be required to dissect this further.

Cardiovascular Adverse Reactions During Antidepressant Treatment: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2010

Background: Antidepressants (ADs) are known to have the potential to cause various cardiovascular adverse drug reactions (ADRs). The tricyclic antidepressants (TCAs) were first revealed to be a possible source of cardiovascular ADRs. In recent years, newer classes of ADs were also suggested to have a higher risk of cardiovascular adverse effects. In particular, the selective serotonin reuptake inhibitors (SSRIs) were suspected to have the potential to induce QTc interval prolongation, and therefore increase the risk of ventricular arrhythmia. This descriptive study is based on the continuous pharmacovigilance program of German-speaking countries (Austria, Germany, and Switzerland), the Arzneimittelsicherheit in der Psychiatrie (AMSP), which assesses severe ADRs occurring in clinical routine situations. Methods: Of 169 278 psychiatric inpatients treated with ADs between 1993 and 2010, 198 cases of cardiovascular ADRs (0.12%) were analyzed. Results: Our study showed that the incidence rates of cardiovascular ADRs were highest during treatment with monoamine oxidase inhibitors (0.27%), TCAs (0.15%), and serotonin noradrenaline reuptake inhibitors (0.14%); the risk of occurring during treatment with SSRIs (0.08%) was significantly lower. The noradrenergic and specific serotonergic AD mirtazapine (0.07%) had a significantly lower risk of cardiovascular ADRs than all other ADs. Severe hypotension was the most frequent ADR, followed by hypertension, arrhythmia, and in some rare cases heart failure. Conclusions: Despite certain limitations due to the AMSP study design, our observations on cardiovascular ADRs can contribute to a better knowledge of the cardiovascular risk profiles of antidepressants in the clinical routine setting. However, prospective studies are needed to verify our findings.

Increase of antipsychotic medication in depressive inpatients from 2000 to 2007: results from the AMSP International Pharmacovigilance Program.

While international guidelines recommend monotherapy with antidepressants for depressed patients, recent investigation has demonstrated augmenting effects of antipsychotics (APs) in patients with major depression. We set out to investigate the use of APs in a European sample of depressed inpatients and the possible changes in their prescription over the period from 2000 to 2007. On two reference days in the years 2000 (32 psychiatric institutions, N=1078) and 2007 (54 psychiatric institutions, N=1826), the following data were recorded for all depressed inpatients (ICD-10: F32.00, F32.01, F32.1, F32.10, F32.11, F32.2, F33.0, F33.00, F33.01, F33.1, F33.10, F33.11, F33.2), monitored as part of the AMSP (Arzneimittelsicherheit in der Psychiatrie) surveillance programme: age, sex, ICD-10 diagnosis and all medication applied on that day. Depressed inpatients with psychotic symptoms were excluded. We found a significant increase in the number of AP-treated inpatients from 37.9% in 2000 to 45.8% in 2007 (χ²=17.257, p<0.001). The number of inpatients who received an atypical AP rose significantly between 2000 and 2007, from 12.8% to 28.3% (χ²=93.37, p<0.001). On the contrary, the percentage of inpatients receiving typical APs showed a significant decrease from 30.2% to 24.1% over the same period (χ²=13.179, p<0.001). Examining only the subgroup of severely depressed inpatients we found an increase in the number of AP-treated inpatients, but this was not statistically significant (χ²=2.047, p=0.15). Our study revealed a significant increase in the usage of atypical APs. However, this effect was not only due to augmentation strategies for severely depressed inpatients. Further studies are needed to examine possible putative effects of AP augmentation treatment in mild to moderate depression.

Influence of family history of major depression, bipolar disorder, and suicide on clinical features in patients with major depression and bipolar disorder

The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide—considered both separately and together—on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed.

Epidemiology and socioeconomic impact of seasonal affective disorder in Austria

BACKGROUNDnSeasonal affective disorder (SAD) is a subtype of recurrent depressive or bipolar disorder that is characterized by regular onset and remission of affective episodes at the same time of the year. The aim of the present study was to provide epidemiological data and data on the socioeconomic impact of SAD in the general population of Austria.nnnMETHODSnWe conducted a computer-assisted telephone interview in 910 randomly selected subjects (577 females and 333 males) using the Seasonal Health Questionnaire (SHQ), the Seasonal Pattern Assessment Questionnaire (SPAQ), and the Sheehan Disability Scale (SDS). Telephone numbers were randomly drawn from all Austrian telephone books and transformed using the random last digits method. The last birthday method was employed to choose the target person for the interviews.nnnRESULTSnOut of our subjects, 2.5% fulfilled criteria for the seasonal pattern specifier according to DSM-5 and 2.4% (95% CI=1.4-3.5%) were diagnosed with SAD. When applying the ICD-10 criteria 1.9% (95% CI=0.9-2.8%) fulfilled SAD diagnostic criteria. The prevalence of fall-winter depression according to the Kasper-Rosenthal criteria was determined to be 3.5%. The criteria was fulfilled by 15.1% for subsyndromal SAD (s-SAD). We did not find any statistically significant gender differences in prevalence rates. When using the DSM-5 as a gold standard for the diagnosis of SAD, diagnosis derived from the SPAQ yielded a sensitivity of 31.8% and a specificity of 97.2%. Subjects with SAD had significantly higher scores on the SDS and higher rates of sick leave and days with reduced productivity than healthy subjects.nnnCONCLUSIONSnPrevalence estimates for SAD with the SHQ are lower than with the SPAQ. Our data are indicative of the substantial burden of disease and the socioeconomic impact of SAD. This epidemiological data shows a lack of gender differences in SAD prevalence. The higher rates of females in clinical SAD samples might, at least in part, be explained by lower help seeking behaviour in males.

Metabolic changes in first-episode early-onset schizophrenia with second-generation antipsychotics.

Individuals with a diagnosis of schizophrenia have a reduced life expectancy compared with the general population and cardiovascular disease is the major contributor to this early mortality. The use of second‐generation antipsychotic (SGA) medications is associated with significant weight gain and metabolic side effects; however, there is limited knowledge in certain diagnostic groups, specifically early‐onset schizophrenia (EOS). This study aimed to investigate the metabolic side effects of SGAs, specifically olanzapine, risperidone and quetiapine, in a cohort of drug‐naïve children and adolescents with first‐episode EOS.

Administration of ketamine for unipolar and bipolar depression

Abstract Objective: Clinical trials demonstrated that ketamine exhibits rapid antidepressant efficacy when administered in subanaesthetic dosages. We reviewed currently available literature investigating efficacy, response rates and safety profile. Methods: Twelve studies investigating unipolar, seven on bipolar depression were included after search in medline, scopus and web of science. Results: Randomized, placebo-controlled or open-label trials reported antidepressant response rates after 24u2009h on primary outcome measures at 61%. The average reduction of Hamilton Depression Rating Scale (HAM-D) was 10.9 points, Beck Depression Inventory (BDI) 15.7 points and Montgomery-Asberg Depression Rating Scale (MADRS) 20.8 points. Ketamine was always superior to placebo. Most common side effects were dizziness, blurred vision, restlessness, nausea/vomiting and headache, which were all reversible. Relapse rates ranged between 60% and 92%. To provide best practice-based information to patients, a consent-form for application and modification in local language is included. Conclusions: Ketamine constitutes a novel, rapid and efficacious treatment option for patients suffering from treatment resistant depression and exhibits rapid and significant anti-suicidal effects. New administration routes might serve as alternative to intravenous regimes for potential usage in outpatient settings. However, long-term side effects are not known and short duration of antidepressant response need ways to prolong ketamine’s efficacy.

Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program

Background: Drug-induced liver injury is a common cause of liver damage and the most frequent reason for withdrawal of a drug in the United States. The symptoms of drug-induced liver damage are extremely diverse, with some patients remaining asymptomatic. Methods: This observational study is based on data of Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries (Austria, Germany, and Switzerland) recording severe drug reactions in psychiatric inpatients. Of 184234 psychiatric inpatients treated with antidepressants between 1993 and 2011 in 80 psychiatric hospitals, 149 cases of drug-induced liver injury (0.08%) were reported. Results: The study revealed that incidence rates of drug-induced liver injury were highest during treatment with mianserine (0.36%), agomelatine (0.33%), and clomipramine (0.23%). The lowest probability of drug-induced liver injury occurred during treatment with selective serotonin reuptake inhibitors ([0.03%), especially escitalopram [0.01%], citalopram [0.02%], and fluoxetine [0.02%]). The most common clinical symptoms were nausea, fatigue, loss of appetite, and abdominal pain. In contrast to previous findings, the dosage at the timepoint when DILI occurred was higher in 7 of 9 substances than the median overall dosage. Regarding liver enzymes, duloxetine and clomipramine were associated with increased glutamat-pyruvat-transaminase and glutamat-oxalat-transaminase values, while mirtazapine hardly increased enzyme values. By contrast, duloxetine performed best in terms of gamma-glutamyl-transferase values, and trimipramine, clomipramine, and venlafaxine performed worst. Conclusions: Our findings suggest that selective serotonin reuptake inhibitors are less likely than the other antidepressants, examined in this study, to precipitate drug-induced liver injury, especially in patients with preknown liver dysfunction.