Interaction between catechol-O-methyltransferase (COMT) Val158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli.

BACKGROUND: Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing. METHOD: A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence. RESULTS: We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing. CONCLUSIONS: Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.

Adolescent depression: clinical features and therapeutic strategies.

BACKGROUND: Major depressive disorder (MDD) is a common disorder during adolescence and it is associated with an increased risk of suicide, poor school performance, impaired social skills, social withdrawal and substance abuse. Further, as many depressive episode in adolescents do not reach the diagnostic threshold for MDD, the disorder remains undetected. AIM: This review aims to provide an update of clinical features of adolescent MDD and to focus on the most appropriate therapeutic strategies to adopt in clinical practice. MATERIALS AND METHODS: We reviewed the international literature to identify studies focusing on clinical features and therapeutic options in adolescents affected by MDD. PubMed, Medline and Cochrane Library databases were searched for English language papers. RESULTS: The clinical picture of depression is variable with sex and age. Somatic complaints, particularly headache and fatigue, are a common presentation in adolescent MDD. Irritability is present most frequently in female and it is related to the severity of MDD. Adolescent MDD is also characterized by a high rates of suicides. The therapeutic strategy in adolescent depression includes psychotropic medications, psychotherapy or a combination of both treatments, with selection of the most appropriate strategy depending on symptom severity. As first-line treatment the traditional cognitive behavioural therapy (CBT), as well as the cognitive Post-Rationalist (PR) approach, are so far considered the goal standard. CONCLUSIONS: The therapeutic approach to the adolescent affected by MMD should respect the person in his/her psycho-physical entirety. The intervention may help the subject in seeking a more stable and adaptable identity. It is relevant to have a good knowledge of the peculiar clinical picture of adolescent MDD in order to make an early identification of the disorder and to define an appropriate personalized therapeutic program.

Postpartum pain in relation with Personal Meaning Organization.

AIM: The aim of this study was to investigate the relationship between postpartum pain and personality considered as Personal Meaning Organization (PMO). Pain diseases, not related to organic disorders, frequently occur in postpartum and may lead to severe consequences for women and their functions of caregiving. Emotions are usually experienced in the body and their expression is strictly related to individual personality. Considering personality as a process, each symptom expresses a need to maintain the sense of oneness and historical continuity. METHODS: One-hundred and five women were enrolled from the Department of Obstetrics and Gynecology and after delivery they presented postpartum pain not related to organic diseases. Women filled out a general information questionnaire assessing age, employment, marital status, education level, parity, type of delivery, attendance to a prepartum course, week of gestation. Their personality, as PMO, was evaluated using the Mini Questionnaire of Personal Organization (MQPO). RESULTS: Controller PMO perceived more pain compared to the Principle Oriented PMO (95% CIs [-0.09, -1.98]; Wald Z=-2.28; P<0.02), slightly more than contextualized patients (95% CIs [-0.09, -1.15]; Wald Z=-1.81, P<0.06) and more than those with a Detached PMO (95% CIs [-0.09, -2.10]; Wald Z=-1.84, P<0.06). CONCLUSION: The results suggest a role of PMO in influencing the perception of postpartum pain and no relation with the other general information assessed, particularly, within the controller women group in which the experience of physical pain might be a way to represent a subjective discomfort.

Antidepressant drug prescribing in general practice: a 6-year study.

We analysed antidepressant drugs (AD) prescription ratios of the GPs working in Verona, Italy, over a 6-year period (1983-1988). The data, provided by a local drug information system (SIF-USL), were calculated as Defined Daily Dose (DDD), which is the unit of drug consumption recommended by WHO. We found that DDD/1000 patients/day increased over the period, mainly because of an increase in the use of 'second-generation' antidepressants and other non-tricyclic antidepressants. An increase in the levels of prescription of AD was observed over the 6 years. This increase was statistically significant when comparing the first (1983) with the other years. Low correlations were found between DDD/patient/year ratios and GPs' age, sex and list size. Harmonic analysis of the seasonal variations in prescriptions of AD revealed a substantial pattern of seasonality, in which the first four harmonics accounted for the greater part (95.5%) of the seasonality. AD prescribing may be linked more closely to seasonal holiday patterns than to seasonality in the onset of depressive disorders.

The management of affective disorders in the community.

Using two systems which routinely record information about the management of psychiatric disorders in the community (a drug prescription monitoring system and a psychiatric case register), a parallel study was conducted in South Verona on antidepressant prescriptions written by general practitioners (GPs) and on contacts for affective disorders with specialized psychiatric services, in 1983 and 1984. The extent of patient contact for affective disorders was approximately ten times greater at the GP level (in one year about 150 antidepressant prescriptions per 1000 adult inhabitants) than at the out-patient/community psychiatric service level. Similarly, the extent of patient contact at the latter level was approximately ten times greater than at the in-patient level. Patients with a diagnosis of affective disorder accounted for about 20% of the total number of patients contacting the specialized services in one year. The proportions of patients admitted to hospital, among those in contact with these services and assigned a diagnosis of depressive neurosis or a diagnosis of affective psychosis, were 34 and 33% (in 1983 and 1984) and 49 and 50% (in 1983 and 1984), respectively. There was a clear correspondence between monthly fluctuations in the extent of care for affective disorders provided at the two levels in 1984, but not in 1983.

Psychotropic drug prescription in general practice in Italy: a two-week prevalence study.

A study on psychotropic drug monitoring was carried out in Verona over a 2-week period using information obtained during consultation with 3 GPs. Psychotropic drugs accounted for 23.4% and 24.3% of all prescriptions in men and women respectively. Benzodiazepines were the most frequently prescribed: 76% and 72% of all psychotropic prescriptions respectively in women and in men. No significant association between psychotropic drug prescription and age, sex, marital status and occupation was found in the present survey. In men only, those patients with higher educational level were more likely to receive a prescription for psychotropic drugs than those with a lower educational level. About 70% of men and 60.4% of women diagnosed by the GP as having a psychiatric problem were prescribed a psychotropic drug. However, the probability of a psychotropic being prescribed, when a psychiatric problem is identified by the GP, was significantly higher (p less than 0.05) in men than in women: odds ratio 39.37 and 16.33 respectively. Psychotropic drugs were prescribed in 35% of men and in about 48% of women in which a social problem was identified by the GP. Women were about 5 times more likely to receive a prescription than men: odds ratio 12 and 2.75 respectively. A significant influence of physical ill-health and educational level on psychotropic prescription emerged: both effects were independent of sex, psychiatric morbidity and social problems. Using a logistic regression analysis, an interactive effect between sex and conspicuous psychiatric morbidity and between sex and social problems was also found.

Provision of mental health care in general practice in Italy.

The main features of the psychiatric system and of the general practice system in Italy since the psychiatric reform and the introduction of a national health service are briefly described. Research conducted in Italy confirms that a large proportion of patients seen by general practitioners have psychological disorders and that only some of those patients whose psychological problems are identified by general practitioners are referred to specialist psychiatric care. Thus, the need to identify the best model of collaboration between psychiatric services and general practice services is becoming increasingly urgent. The chances of improving links between the two services and of developing a satisfactory liaison model are probably greater in countries such as Italy where psychiatric services are highly decentralized and community-based, than in countries where the psychiatric services are hospital-based.

[Hypnotic drugs in a population. Prescriptions by the specialist and the general practitioner]. / I farmaci ipnotici nella popolazione. La prescrizione dello specialista e del medico di base.

The aims of our survey were to estimate the prevalence of hypnotic drug prescription in a representative sample of population in 5 cities of Northern Italy and to analyse the pattern of prescription of these drugs by general practitioners (GPs) and psychiatrists. The data were collected with the collaboration of pharmacists working in 145 pharmacies. All consecutive patients presenting a prescription for a hypnotic drug were interviewed by the pharmacists during a two-week period. The pharmacists interviewed 7744 consecutive patients. The highest prevalence of prescriptions for hypnotic drugs was found in the elderly and in women. The majority of prescriptions were for benzodiazepines (BDZ), with lorazepam and triazolam accounting for about 50% of the total prescriptions. Short-acting and ultra-short-acting BDZ were more frequently prescribed for sleep induction by GPs than by psychiatrists. Approximately 73% of subjects reported that they had been taking the prescribed drug for one year or more. The high proportion of long-term BDZ users may be a consequence of the short period surveyed, which produced data weighted toward long-term consumption. Our data, however, do not permit to establish whether long-term use is appropriate from a clinical point of view or is the consequence of a physical dependence. We must be aware that this practice needs to be studied more accurately, with the aim to assess the risk/benefit ratio of long-term BDZ use.

Inflammatory and neurodegenerative pathways in depression: a new avenue for antidepressant development?

The latest advancement in neurobiological research provided an increasing evidence that inflammatory and neurodegenerative pathways play a relevant role in depression. Preclinical and clinical studies on depression highlighted an increased production of inflammatory markers, such as interleukin (IL)-1, IL-6, tumor necrosis factor-α and interferon- α and γ. On the other hand, acute and chronic administration of cytokines or cytokine inducers were found to trigger depressive symptoms. According to the cytokine hypothesis, depression would be due to a stress-related increased production of pro-inflammatory cytokines that, in turn, would lead to increased oxidative and nitrosative brain damage and to indoleamine 2,3 dioxygenase (IDO) induction, with production of tryptophan (TRP) catabolites along the IDO pathway (TRYCATs) and consequent reduced availability of TRP and serotonin (5-HT). Cytokines would also play a role in the onset of the glucocorticoid resistance, underlying the overdrive of the hypothalamic-pituitary-adrenal axis. Therefore, the activation of the inflammatory and neurodegenerative pathways would lead to the brain damage observed in depression through both reduced neurogenesis and increased neurodegeneration. Besides the 5-HT system, other targets, possibly within the I&ND pathways, should be considered for the future treatment of depression: cytokines and their receptors, intracellular inflammatory mediators, IDO, TRYCATs, glucocorticoid receptors, neurotrophic factors may all represent possible therapeutic targets for novel antidepressants. In addition, it should be also clarified the role of the existing anti-inflammatory drugs in the treatment of depression, and those compounds with the anti-inflammatory and anti-oxidative properties should be examined either as monotherapy or adjunctive therapy. In conclusion, the molecular inflammatory and neurodegenerative pathways might provide new targets for antidepressant development and might be crucial to establish a rational treatment of depression aimed, hopefully, to its causal factors.

SSRIs during breastfeeding: spotlight on milk-to-plasma ratio.

OBJECTIVE: To investigate the usefulness of the milk-to-plasma (M/P) ratio for assessing the risks for the breastfed infant associated with the maternal use of SSRIs. DATA SOURCES: Medline, Toxnet, Embase, Current Contents, and PsycInfo indexed articles from 1980 to September 2006. STUDY SELECTION AND DATA EXTRACTION: All studies reporting the M/P ratio in mothers taking SSRIs while breastfeeding or studies which such an information could be calculated from data reported in the article. DATA SYNTHESIS: Higher M/P ratios were rarely associated with a clinically significant impact on the babies during the early phases of breastfeeding. CONCLUSIONS: So far no evidence-based information seems to support the hypothesis that SSRIs characterized by a M/P ratio <1.0 should be preferred. Hence, physicians should consider different parameters when attempting to choose the safest SSRI for the breastfeeding woman. These parameters might be represented by the number of well-documented published adverse event reports and the tendency of each SSRI of inducing in the infants serum concentrations that are elevated above 10% of average maternal serum levels. In any case, if the mother wishes to breastfeed her infant while taking a SSRI, the baby should be closely monitored in order to promptly detect any iatrogenic event.

Performance of the Italian version of the subjective well-being under neuroleptic (SWN) scale in schizophrenic outpatients.

BACKGROUND: Several studies indicate that subjective experience toward antipsychotic drugs (APs) in schizophrenic patients is a key factor in ensuring a smooth recovery from the illness. OBJECTIVE: The principal aim of this study was to establish the psychometric performance of the Subjective Well-being Under Neuroleptic (SWN) scale in its Italian version and to assess, through the SWN scale, the subjective experience of stabilized psychotic outpatients in maintenance with APs. METHODS: The original short version of SWN, consisting of 20 items, was back translated, and a focus group was also conducted to better improve the comprehension of the scale. RESULTS: The results showed a good performance of the Italian version of the SWN as documented by the internal consistency (Cronbach's alpha; 0.85). A satisfactory subjective experience was reported in the sample of schizophrenic outpatients interviewed (SWN mean total score: 84.95, SD: 17.5). CONCLUSIONS: The performance of the SWN scale in the present study was very similar to that reported by Naber et al. in the original validation study. Large multi-center studies are needed to better establish differences in the subjective experience of schizophrenic patients treated with first- and second-generation APs.

Drug treatment of panic disorder--a critical review of controlled clinical trials.

The clinical efficacy of drug treatment for panic disorder has been evaluated in several studies, especially in the last decade. In this paper we reviewed double-blind controlled clinical trials of antidepressants and benzodiazepines in the treatment of panic disorder. Tricyclic antidepressants (principally imipramine) and benzodiazepines were equally effective in reducing panic symptomatology. This evidence does not support the hypothesis that panic-related symptomatology is a psychopathological entity, requiring a specific antidepressant drug treatment. The combination of psychological therapy with drug treatment was associated with even better outcome. On the other hand, the efficacy of MAOI remains to be demonstrated. Better compliance with benzodiazepines may favor the clinical use of these drugs rather than antidepressants. However, more prospective controlled studies including follow-up examinations are required, in order to assess the risk/benefit ratio of these treatments after long-term therapy.

Psychiatric morbidity in general practice in Italy. A point-prevalence survey in a defined geographical area.

Psychiatric morbidity among 505 attenders on a single day at 32 general practices in South Verona was assessed using the General Health Questionnaire (GHQ-30) and recordings of practitioners' evaluations. The usual GHQ scoring system with a cut-off point of 5/6 resulted in 52% of high-scorers while the scoring system for longstanding psychological distress conditions (C-GHQ) yielded 37% of high-scorers (cut-off point 11/12). General practitioners identified 28% of attenders as cases. One-day population based prevalence estimates for the GHQ-30 and practitioners' assessment gave values of 6.6 and 4.5 per 1000 at risk. Among several possible risk factors, only presence of previous psychiatric illness increased significantly the relative risk of being a case in terms of GHQ, C-GHQ scores and practitioners' assessments. These findings are discussed in relation to the results of other surveys in the same area and other general practice studies.

[En epidemiologic approach for the analysis of the demand and supply of psycho-psychiatric care in general medicine and in specialized services]. / Un approccio epidemiologico per l'analisi della domanda e dell'offerta di assistenza psicologico-psichiatrica nella medicina di base e nei servizi specialistici.

In this paper we present data collected in the area of Verona concerning indicators of demand and of supply of care in two settings, the general practice and the South-Verona Community Psychiatric Service. These data, obtained from the epidemiological studies conducted by our research group during the past ten years, emphasize similarities and differences existing in the two levels of care. In general practice the demand for care for psychological disorders is difficult to identify, because of the frequent somatic expression of these disorders; moreover at the level of psychiatric services the demand is frequently aspecific. As far as the supply of care is concerned, in both settings drug prescription is the most frequent treatment, however other interventions are also offered. For example, in general practice counselling and referral to the psychiatrist are often provided; in psychiatric services monitored during our studies a large range of treatments were supplied, often in an integrated way.

Psychiatric morbidity in an Italian general practice.

A two-stage screening strategy was applied in a single-handed general practice in northern Italy. The study was designed so that all the second-stage psychiatric interviews were conducted during the first phase of the study (group A patients), while self-report questionnaire (GHQ) and GP assessments only were collected during the second phase (group B patients). The estimated true case rate of psychiatric disorder (36%) did not differ between the two phases of the study, but there were marked differences in the general practitioner's diagnostic behaviour. During the first phase (when psychiatric interviews were being conducted in the practice), her behaviour was heavily biased towards diagnosing psychiatric disorder; 61% of the patients were regarded by her as psychiatric cases and the hidden psychiatric morbidity rate was only 9%. During the second phase of the study (no psychiatric interviews in the practice), only 37% of the patients were regarded as psychiatric cases by the GP, and the hidden morbidity rate was 59%. The results are interpreted as demonstrating that the presence of a psychiatrist conducting a two-stage screening survey in the practice had a profound effect on the diagnostic threshold. They also provide support for the use of the GHQ as a case-finding instrument in general practice.

Patterns of hypnotic drug prescription in Italy. A two-week community survey.

BACKGROUND: In Italy a number of studies have been published on psychotropic drug use in general practice and community settings. However, the present study is the first Italian study to focus on hypnotic drug prescriptions in a large community sample. METHOD: Data were collected from 145 of the total of 404 pharmacies of five large cities in north-eastern Italy. All consecutive patients presenting a prescription for a hypnotic drug were interviewed by the pharmacists during a two-week period. RESULTS: The pharmacists interviewed 7/44 consecutive patients. The highest prevalence of prescriptions for hypnotic drugs was found in the elderly and in women. The majority (96%) of prescriptions were for benzodiazepines, with lorazepam and triazolam accounting for 50%. Short-acting and ultra-short-acting benzodiazepines were more frequently prescribed for sleep induction by general practitioners (GPs) than by psychiatrists and other physicians. Frequently the benzodiazepine used as a hypnotic was also prescribed for day time sedation. Approximately 72% of subjects reported they had been taking the prescribed drug for one year or more. CONCLUSIONS: In Italy benzodiazepines are the most frequently prescribed drugs for sleep induction; as they are widely prescribed for elderly people by GPs often for long periods of time, educational programmes and guidelines on the rational use of benzodiazepines in general practice are needed.

Psychotropic drug use in Italy: national trends and regional differences.

Psychotropic drug sales data for Italy were examined for the years 1975-84. The principal findings were of more-or-less consistent annual increases in sales of antidepressants, minor tranquillizers and, to a lesser extent, of neuroleptics. These trends are interpreted in the context of the characteristics of the Italian National Health Service (NHS), and in relation to findings from psychotropic drug utilization studies in other Western countries. Regional differences in psychotropic drug sales for 1983/4 were also examined. Marked differences were found and, in general, levels of use were higher in North/Central Italy than in the South. Factors influencing regional differences were explored using regression analysis. Regional NHS expenditure (excluding that on drugs) was found to influence strongly the sales of all categories of psychotropic drug, whereas there was also a marked urban greater than rural difference in the sales of tranquillizers.

Meta-analysis of double-blind placebo-controlled trials of antidepressants and benzodiazepines for patients with panic disorders.

Meta-analysis of 19 double-blind placebo-controlled trials of antidepressants (N = 13) and benzodiazepines (N = 6) for patients with panic disorders showed that active treatment had 25% greater success rate than placebo over a mean duration of 14 weeks. There were no statistically significant differences observed between treatment sub-groups (antidepressants--mean duration 16 weeks; and benzodiazepines--mean duration 7 weeks). On this basis antidepressants and benzodiazepines prescribed in clinical settings are likely to be equally effective in the short-term treatment of people with panic disorders.