Advanced molecular approaches in male infertility diagnosis†.

In the recent years a special attention has been given to a major health concern namely to male infertility, defined as the inability to conceive after 12 months of regular unprotected sexual intercourse, taken into account the statistics that highlight that sperm counts have dropped by 50-60% in recent decades. According to the WHO, infertility affects approximately 9% of couples globally, and the male factor is believed to be present in roughly 50% of cases, with exclusive responsibility in 30%. The aim of this article is to present an evidence-based approach for diagnosing male infertility that includes finding new solutions for diagnosis and critical outcomes, retrieving up-to-date studies and existing guidelines. The diverse factors that induce male infertility generated in a vast amount of data that needed to be analyzed by a clinician before a decision could be made for each individual. Modern medicine faces numerous obstacles as a result of the massive amount of data generated by the molecular biology discipline. To address complex clinical problems, vast data must be collected, analyzed, and used, which can be very challenging. The use of artificial intelligence (AI) methods to create a decision support system can help predict the diagnosis and guide treatment for infertile men, based on analysis of different data as environmental and lifestyle, clinical (sperm count, morphology, hormone testing, karyotype, etc.), and "omics" bigdata. Ultimately, the development of AI algorithms will assist clinicians in formulating diagnosis, making treatment decisions, and predicting outcomes for assisted reproduction techniques.

NGS and phenotypic ontology-based approaches increase the diagnostic yield in syndromic retinal diseases.

Syndromic retinal diseases (SRDs) are a group of complex inherited systemic disorders, with challenging molecular underpinnings and clinical management. Our main goal is to improve clinical and molecular SRDs diagnosis, by applying a structured phenotypic ontology and next-generation sequencing (NGS)-based pipelines. A prospective and retrospective cohort study was performed on 100 probands with an a priori diagnosis of non-Usher SRDs, using available clinical data, including Human Phenotype Ontology annotation, and further classification into seven clinical categories (ciliopathies, specific syndromes and five others). Retrospective molecular diagnosis was assessed using different molecular and bioinformatic methods depending on availability. Subsequently, uncharacterized probands were prospectively screened using other NGS approaches to extend the number of analyzed genes. After phenotypic classification, ciliopathies were the most common SRD (35%). A global characterization rate of 52% was obtained, with six cases incompletely characterized for a gene that partially explained the phenotype. An improved characterization rate was achieved addressing prospective cases (83%) and well-recognizable syndrome (62%) subgroups. The 27% of the fully characterized cases were reclassified into a different clinical category after identification of the disease-causing gene. Clinical-exome sequencing is the most appropriate first-tier approach for prospective cases, whereas whole-exome sequencing and bioinformatic reanalysis increases the diagnosis of uncharacterized retrospective cases to 45%, mostly those with unspecific symptoms. Our study describes a comprehensive approach to SRDs in daily clinical practice and the importance of thorough clinical assessment and selection of the most appropriate molecular test to be used to solve these complex cases and elucidate novel associations.

Why not the best? Social anxiety symptoms and perfectionism among Israeli Jews and Arabs: a comparative Study.

BACKGROUND: Social Anxiety Disorder (SAD) has been repeatedly shown to be very prevalent in the Western society and is characterized by low self-esteem, pessimism, procrastination and also perfectionism. Very few studies on SAD have been done in the Middle East or in Arab countries, and no study tackled the relationship between social anxiety symptoms and perfectionism in non-Western samples. METHODS: We examined social anxiety symptoms and perfectionism in a group of 132 Israeli Jewish (IJ) and Israeli Arab (IA) students. Subjects completed the Liebowitz Social Anxiety Scale (LSAS), the Multidimensional Perfectionism Scale (MPS), the Negative Automatic Thoughts Questionnaire (ATQ-N), the Positive Automatic Thoughts Questionnaire (ATQ-P) and a socio-demographic questionnaire. RESULTS: The rate of SAD in our sample according to a LSAS score of 60 or more was 17.2% (IJ=13.8%, IA=19%, ns). The correlation between perfectionism and the LSAS was high in both groups, and in particular in the IJ group. The IA group had higher scores of social avoidance, of ATQ-P and of two of the MPS subscales: parental expectations and parental criticism. Concern over mistakes and negative automatic thoughts positively predicted social fear in the IJ group, whereas in the IA group being female, religious and less educated positively predicted social fear. Negative automatic thoughts and age positively predicted social avoidance in the IJ group. In general, the IJ and IA subjects showed higher social anxiety, higher ATQ-N scores and lower parental expectations as compared with non-clinical US samples. CONCLUSIONS: Social anxiety symptoms and perfectionism are prevalent in Arab and Jewish students in Israel and seem to be closely related. Further studies among non-western minority groups may detect cultural influences on social anxiety and might add to the growing body of knowledge on this intriguing condition.

Paroxetine in panic disorder: clinical management and long-term follow-up.

Panic disorder is one of the most common anxiety disorders and has a lifetime prevalence of 3-5%. Panic attacks can begin at any age, but commonly have their onset in early adulthood between the ages of 20 and 40 years. Naturalistic data has shown that panic disorder has a chronic and relapsing course. Panic disorder is reported to be associated with an increased risk of suicidal behavior and comorbid psychiatric diagnoses such as depression and substance abuse. Currently, recommended treatment modalities for panic disorder include the use of antidepressant pharmacotherapy and/or cognitive behavioral therapy. Paroxetine is unique among the selective serotonin reuptake inhibitors since, in addition to its effect on the CNS serotonergic neurotransmission, it also has mild noradrenergic properties demonstrated to be effective in the treatment of anxiety disorders and depression. Paroxetine treatment has the potential to cause weight gain and sexual dysfunction, primarily anorgasmia and ejaculatory dysfunction for the long term. In the short-term, treatment causes nausea, gastrointestinal disturbances, irritability, headaches and eating and sleeping difficulties. Paroxetine is an example of an selective serotonin reuptake inhibitor agent, which has been well studied in the treatment of panic disorder and is efficacious and well-tolerated. Paroxetine pharmacotherapy has been recommended to be continued for 1 year as specified in the treatment guidelines set by the American Psychiatric Association in the treatment of panic disorder.

The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study.

BACKGROUND AND OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line treatment for panic disorder, although up to 30% of patients either do not respond to SSRIs or withdraw due to adverse events. Reboxetine, a selective norepinephrine reuptake inhibitor (selective NRI), is effective in treating depression and may alleviate depression-related anxiety. This study aimed to investigate the efficacy of reboxetine in the treatment of patients with panic disorder who did not respond to SSRIs. METHOD: In this 6-week, open-label study, 29 adult outpatients with panic disorder who had previously failed to respond to SSRI treatment received reboxetine 2 mg/day, titrated to a maximum of 8 mg/day over the first 10 days. Efficacy was assessed using the Panic Self-Questionnaire (PSQ), the Hamilton Rating Scale for Anxiety (HAM-A), the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global Assessment of Functioning (GAF) Scale. RESULTS: The 24 patients who completed the study responded well to reboxetine treatment. Significant improvement (p < 0.001) was observed in the number of daily panic attacks, and on the scales measuring anxiety, depression and functioning. Reboxetine was generally well tolerated. Five patients withdrew due to adverse events. CONCLUSIONS: Reboxetine appears to be effective in the treatment of SSRI-refractory panic disorder patients and warrants further clinical investigation.

Psychoeducation in panic disorder patients: effect of a self-information booklet in a randomized, masked-rater study.

The aim of our study was to evaluate the effectiveness of a self-information booklet (SIB) in decreasing anxiety and panic attacks in Panic Disorder (PD) patients. Eighty-four patients attending an outpatient clinic due to panic disorder were randomly chosen to receive paroxetine with/without a friendly-designed brochure. Follow-up was done by a masked rater after 1, 3,and 12 weeks in order to evaluate whether the co-administration of paroxetine and the brochure (Group A) had a beneficial effect over the administration of paroxetine alone (Group B). After 3 weeks of therapy, Group A patients had significantly greater improvement and lower scores on the Hamilton Anxiety Scale, the Panic Self Questionnaire, and the Visual Analog Scale. After 12 weeks, the differential improvement was not statistically significant and both groups had improved as compared to baseline. The administration of a psychoeducational brochure (SIB) to PD patients at the initiation of therapy had beneficial effects during the first weeks of treatment. Although this effect fades away, the role of the SIB is overstressed in its ability to increase well being and compliance, and reduce anxiety and panic attacks.

Alexithymia and suicidality in panic disorder.

To evaluate the prevalence of suicidal behavior in patients with panic disorder (PD) and to study the role of alexithymia (AL), an affect component, as a predictor of suicidal behavior in PD, we compared 42 patients with PD with or without agoraphobia with 24 healthy controls with regards to depression, AL and suicide risk. Only 5% of the PD patients reported previous suicide attempts. A higher frequency of positive AL (score > 73) was found among the PD patients (39% v 4% among the controls). PD patients had a higher suicide risk and AL as compared to controls, but only the increased suicide risk reached statistical significance. AL subjects had higher suicide risk scores as compared to non-AL subjects. Significant correlations were found between the AL score and suicide risk, although the most significant correlation was, as expected, between the depression level and the suicide risk. A low rate of previous suicide attempts was found in the PD group, perhaps reflecting the low comorbidity in our sample. We suggest that AL may have a role in the causation of suicidal behavior in PD patients, although further studies should re-examine this issue with larger samples.

A review of psychological debriefing after extreme stress.

Preventive intervention after exposure to traumatic events is a subject of increasing interest among mental health professionals. Psychological debriefing, which aims to reduce the risk of posttraumatic stress disorder and other psychopathological sequelae of traumatic experiences, is an example of such an intervention. The authors review the history of psychological debriefing and examine its efficacy. They conclude that psychological debriefing might be an effective intervention after extreme stress, although more support from controlled studies is required.

Anger, impulsivity, social support, and suicide risk in patients with posttraumatic stress disorder.

An emerging literature suggests that posttraumatic stress disorder (PTSD) patients are at an increased risk for suicide. The objective of this study was: a) to reexamine the relationship between PTSD and suicide by comparing suicide risks of persons with PTSD, to persons with anxiety disorder and to matched controls; and b) to examine the relationship between anger, impulsivity, social support and suicidality in PTSD and other anxiety disorders. Forty-six patients suffering from PTSD were compared with 42 non-PTSD anxiety disorder patients and with 50 healthy controls on measures of anger, impulsivity, social support, and suicide risk. Persons with PTSD had the highest scores on the measures of suicide risk, anger, and impulsivity and the lowest scores on social support. Multivariate analysis revealed that in the PTSD group, impulsivity was positively correlated with suicide risk and anger was not. PTSD symptoms of intrusion and avoidance were only mildly correlated with suicide risk at the bivariate level but not at the multivariate level. For the PTSD and anxiety disorder groups, the greater the social support, the lower the risk of suicide. For the controls, social support and impulsivity were not related to suicide risk, whereas anger was. These findings suggest that persons with PTSD are at higher risk for suicide and that in assessing suicide risk among persons with PTSD, careful attention should be paid to levels of impulsivity, which may increase suicide risk, and to social support, which may reduce the risk.

Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial.

The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder (PD). Twenty-five outpatients having PD with or without agoraphobia were included. These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day. Treatment-resistant PD was defined as a less than 20% reduction in score on the Panic Self-Questionnaire (number of attacks per week) (PSQ) and the Clinical Anxiety Scale With Panic Attacks (CAS+PA). These patients continued to receive fluoxetine 20 mg/day and were randomly assigned to additionally receive either pindolol (2.5 mg three times daily) or placebo for the following 4 weeks. Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression (HAM-D), the CAS+PA, the NIMH Anxiety Scale, the PSQ, and the Clinical Global Impression Scale. The data were analyzed using a repeated-measures analysis of variance (ANOVA) and a t-test for independent samples. Patients treated with the combination of pindolol and fluoxetine (N = 13) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales, with the exception of HAM-D. The statistical differences were shown using the repeated-measures ANOVA (baseline, week 2, week 4) and also with t-tests from the second week of the trial. These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD.

Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial.

OBJECTIVE: To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. METHOD: Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. RESULTS: Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. CONCLUSIONS: The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.

Alexithymia, affect intensity and emotional range in suicidal patients.

BACKGROUND: Although negative affect in general has been widely associated with suicide, the role of specific emotions and affect features in depression and suicidality is unclear. This study examined the potential of three major components of the affect structure as predictors of suicidal behavior. METHODS: Twenty suicidal depressed (SD) inpatients were compared with 20 nonsuicidal depressed (NSD) inpatients and 20 healthy controls for alexithymia, emotional range (ER; i.e. variety of emotions experienced by the subjects) and affect intensity (AI; i.e. the intensity of their emotional responsiveness). RESULTS: Both the SD and the NSD patients had a narrower range of emotions, a stronger AI and a higher degree of alexithymia than did the healthy controls. No differences were found between the scores of the two inpatients groups. CONCLUSIONS: The three affect components examined (alexithymia, AI and ER) did not prove to represent sensitive predictors of suicidal behavior. Hopelessness and depression severity were found to be more reliable in the prediction of suicidal risk. We discuss the implications of this study, particularly the possibility of early detection and intervention in patients at risk.

A double-blind crossover comparison of clomipramine and desipramine in the treatment of panic disorder.

OBJECTIVE: To compare the efficacy of clomipramine hydrochloride (CMI), a serotonin reuptake inhibitor with the noradrenergic tricyclic antidepressant agent, and desipramine hydrochloride (DMI) for patients with panic disorder (PD). METHOD: Following a 2-week, single-blind placebo washout phase, 17 PD outpatients completed a 16-week, double-blind, crossover comparison of CMI and DMI. Key outcome measures included panic attacks frequency, the NIMH Global Scales for Anxiety, Depression and Impairment, Hamilton Anxiety Scale (Psychic and Somatic Subscales), Zung Anxiety Inventory (Raw and Index Subscales) and the Spielberger State Anxiety Scale. RESULTS: Both CMI and DMI led to significant improvement from baseline placebo state in panic attacks frequency and behavioral ratings (p<0.001). CMI led to a greater reduction in the frequency of panic attacks (p=0.028) and was superior to DMI on ratings of anxiety: NIMH Global Anxiety, Zung Anxiety Scale (Raw and Index) and the Spielberger Anxiety Scale. No difference was found between the drugs on the NIMH Global Impairment Scale and the Hamilton Somatic and Psychic Scales. CONCLUSION: Both drugs appeared to have significant therapeutic effects in patients with PD, but CMI appeared to be more effective. The effectiveness of the serotonergic drug suggests that the role of the serotonergic system in the pathogenesis of PD should be further explored.

The treatment of kleptomania with serotonin reuptake inhibitors.

Kleptomania is characterized by an irresistible impulse to steal objects not needed for personal use or for their monetary value. Several recent case reports have shown that Serotonin Specific Reuptake Inhibitors (SSRIs) could be effective in the treatment of kleptomania just as it is in other obsessive-compulsive spectrum disorders. We report five cases of kleptomania patients who were successfully treated with fluoxetine or paroxetine in combination with a psychotherapeutic intervention. In one case, the discontinuation of the medication repeatedly led to the resurgence of the kleptomanic behavior. Our case series illustrates the effectiveness of SSRIs in kleptomania. It thus supports the assumption that this syndrome involves a dysfunctional serotoninergic mechanism.

Camptocormia: a case of possible paraneoplastic aetiology.

We present a patient with gradual development of camptocormia, three years before a non-Hodgkin's lymphoma was diagnosed. Lymphomas are known to produce neuromuscular symptoms through several indirect mechanisms. Recent studies regard camptocormia as a primary disease of the paravertebral muscles. To our knowledge this is the first report associating camptocormia with malignancy. The possibility of a paraneoplastic syndrome is discussed.

Belief in transmigration of the soul and psychopathology in Israeli Druze. A culture-sensitive psychotherapeutic approach.

One of the central tenets of the Druze religion is the transmigration of the soul. In rare cases this belief may be related to psychopathology or cause a temporary inability to function normally. We report on 5 Druze patients whose preoccupation with transmigration was the basis of their pathological behavior. These cases illustrate the interaction between cultural and religious beliefs, and psychopathology, and emphasize the importance of employing a culture-specific psychiatric approach in the management of this type of patients.

Labetalol does not lengthen asystole during electroconvulsive therapy.

Labetalol, a combined alpha- and beta-adrenergic blocker is often used to attenuate the transient increases in heart rate and blood pressure that accompany electroconvulsive therapy (ECT). It has been suggested that labetalol should not be administered during ECT without the protection provided by anticholinergic medications, because of its potential severe bradycardic effects. We present our experience with 32 patients from all age groups who received labetalol without anticholinergic treatment during ECT. None of the patients demonstrated adverse bradycardic effects. We conclude that administration of labetalol during ECT does not routinely require premedication with anticholinergic drugs and does not lengthen asystole.

Vitamin E treatment in tardive dystonia.

Tardive dystonia is a disorder characterized by abnormally sustained posturing associated with the use of dopamine-receptor blocking agents such as antipsychotic drugs. However, the structural pathologic and pathophysiologic features of this disorder are unknown, and no consistently effective pharmacologic treatment is available. Patients with tardive dystonia mostly are young men. We present the case of one substantially improved with treatment by 1200 mg/d (IU) of vitamin E.