Hagop Akiskal

Notwithstanding the emerging literature on comorbidity between obsessive-compulsive disorder (OCD) and bipolar disorder, relatively few systematic data exist on the clinical characteristics of this interface and its treatment. The aim of the present study is to address this challenge as it appears in a setting of routine clinical practice. The sample comprised 68 patients with comorbid DSM-IV diagnoses of OCD and major depressive episode admitted and treated at the day-hospital in the Department of Psychiatry at the University of Pisa (Pisa, Italy) during a 3-year period (January 1995-December 1998). Thirty-eight patients (55.8%) showed lifetime comorbid bipolar disorder (12 [31.6%] bipolar I and 26 [68.4%] bipolar II). Diagnoses and clinical features were collected by means of structured (Structured Clinical Interview for DSM-IV) and semistructured interviews (OCD-Interview). Assessments of drug treatments, clinical outcome, and adverse effects were made prospectively as part of routine clinical care throughout the course of their day-hospitalization. In contrast with non-bipolar OCD patients, OCD-bipolar patients showed a more episodic course with a greater number of concurrent major depressive episodes. They reported a significantly higher rate of sexual obsessions and significantly lower rate of ordering rituals. Furthermore, they reported more frequent current comorbidity with panic disorder-agoraphobia and abuse of different substances (alcohol, sedatives, nicotine, and coffee). Drug treatment with clomipramine and, to a lesser extent, with selective serotonin reuptake inhibitors was associated with hypomanic switches in OCD-bipolar patients, especially in those not concomitantly treated with mood stabilizers. A combination of multiple mood stabilizers was necessary in 16 OCD-bipolar patients (42.1%) and a combination of mood stabilizers with atypical antipsychotics was required in 4 cases (10.5%). OCD-bipolar patients tended to show a less positive outcome for mood symptomatology and general functioning. Three patients required hospitalization for severe mixed episode. In a tertiary care center, comorbidity between OCD and bipolar disorder is a significant clinical problem affecting a large number of patients and has a substantial impact on the clinical characteristics and treatment outcome of both disorders.

The frequency of the association between substance use and psychiatric disorders is higher than what might be expected as a result of chance alone; the most frequently associated psychiatric symptoms, syndromes and disorders pertain to the domains of mood, anxiety and impulsivity. There are several reasons for taking these psychiatric manifestations into account when evaluating clinical presentations of substance-use disorders. DSM nosology does not seem to grasp the complexity of the interaction between the psychic structures involved, and neurobiological and physiopathological processes activated by encounters with substances of abuse. Based on neurobiological, epidemiological and clinical indications, an integrated, unified perspective explaining the pathophysiology and phenomenology of addiction has been proposed. The lack of substantial changes in the approach to the psychiatric comorbidity of addiction in the DSM V, despite the plausibility of the hypothesis that there may be ...

Recent celebrity deaths have been widely reported in the media and turned the public attention to the coexistence of mood, psychiatric and substance-abuse disorders. These tragic and untimely deaths motivated us to examine the scientific and clinical data, including our own work in this area. The self-medication hypothesis states that individuals with psychiatric illness tend to use heroin to alleviate their symptoms. This study examined the correlations between heroin use, mood and psychiatric disorders, and their chronology in the context of dual diagnosis. Out of 506 dual diagnosed heroin addicts, 362 patients were implicated in heroin abuse with an onset of at least one year prior to the associated mental disorder (HER-PR), and 144 patients were diagnosed of mental illness at least one year prior to the associated onset of heroin use disorder (MI-PR). The retrospective cross-sectional analysis of the two groups compared their demographic, clinical and diagnostic characteristics ...

This monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions. Panel discussants agree that current data confirm the utility of CBZ ERC a...

The constructs of atypical depression, bipolar II disorder and borderline personality disorder (BPD) overlap. We explored the relationships between these constructs and their temperamental underpinnings. We examined 107 consecutive patients who met DSM-IV criteria for major depressive episode with atypical features. Those who also met the DSM-IV criteria for BPD (BPD+), compared with those who did not (BPD-), had a significantly higher lifetime comorbidity for body dysmorphic disorder, bulimia nervosa, narcissistic, dependent and avoidant personality disorders, and cyclothymia. BPD+ also scored higher on the Atypical Depression Diagnostic Scale items of mood reactivity, interpersonal sensitivity, functional impairment, avoidance of relationships, other rejection avoidance, and on the Hopkins Symptoms Check List obsessive-compulsive, interpersonal sensitivity, anxiety, anger-hostility, paranoid ideation and psychoticism factors. Logistic regression revealed that cyclothymic temperame...

Considerable evidence has demonstrated that melancholic and atypical major depression have distinct biological correlates relative to undifferentiated major depression, but few studies have specifically delineated neuropsychological performance for them. In a six-week prospective longitudinal study, we simultaneously compared neuropsychological performance among melancholic depression (n=142), atypical depression (n=76), undifferentiated major depression (n=91), and healthy controls (n=200) during a major depressive episode and a clinically remitted state, respectively. We administered neuropsychological tests assessing processing speed, attention, shifting, planning, verbal fluency, visual spatial memory, and verbal working memory to all participants. During the depressive state, the three subtypes displayed extensive cognitive impairment, except for attention, when compared with the healthy controls. Melancholic depression significantly differed from atypical depression in process...

Dementia is a neuropsychiatric disorder characterized by cognitive impairment and behavioral disturbances. The behavioral and psychological symptoms of dementia (BPSD) are common, contributing to caregiver burden and premature institutionalization. Management of BPSD is complex and often needs recourse to psychotropic drugs. Though widely prescribed, there is a lack of consensus concerning their use, and serious side effects are frequent. This is particularly the case with antidepressant treatment based on the assumption that BPSD is depressive in nature. A better understanding of BPSD etiology could lead to better management strategies. We submit that some BPSD could be the consequence of both dementia and an undiagnosed comorbid bipolar spectrum disorder, or a pre-existing bipolar diathesis pathoplastically altering the clinical expression of dementia. The existence of such a relationship is based on clinical observation, as far as the high frequency of bipolar spectrum disorders ...

Post-traumatic stress disorder (PTSD) represents one of the most frequently psychiatric sequelae to earthquake exposure. Increasing evidence suggests the onset of maladaptive behaviors among veterans and adolescents with PTSD, with specific gender differences emerging in the latter. Aims of the present study were to investigate the relationships between maladaptive behaviors and PTSD in earthquake survivors, besides the gender differences in the type and prevalence of maladaptive behaviors and their association with PTSD. 900 residents of the town of L'Aquila who experienced the earthquake of April 6th 2009 (Richter Magnitude 6.3) were assessed by means of the Trauma and Loss Spectrum-Self Report (TALS-SR). Significantly higher maladaptive behavior prevalence rates were found among subjects with PTSD. A statistically significant association was found between male gender and the presence of at least one maladaptive behavior among PTSD survivors. Further, among survivors with PTSD significant correlations emerged between maladaptive coping and symptoms of re-experiencing, avoidance and numbing, and arousal in women, while only between maladaptive coping and avoidance and numbing in men. Our results show high rates of maladaptive behaviors among earthquake survivors with PTSD suggesting a greater severity among men. Interestingly, post-traumatic stress symptomatology appears to be a better correlate of these behaviors among women than among men, suggesting the need for further studies based on a gender approach.

So far there is a scarce of studies dealing with the relationship between different aspects of aggressive behaviour and affective temperaments among various mood disorders. The aim of the present study was to explore in a group of patients with affective mood disorders the relationship between affective temperaments and aggression. 100 consecutive outpatients in euthymic phase of mood disorders (46 with bipolar disorder-type I, 18 with bipolar disorder-type II and 36 with major depressive disorder) were self-assessed with the Aggression Questionnaire and the short version of Slovenian Temperament Evaluation of Memphis, Pisa, Paris and San Diego - Autoquestionnaire (TEMPS-A). The factorial analysis of the TEMPS-A subscales revealed 2 main factors: Factor 1 (prominent cyclothymic profile) consisted of cyclothymic, depressive, irritable, and anxious temperaments and Factor 2 (prominent hyperthymic profile) which was represented by the hyperthymic temperament, and by depressive and anxious temperaments as negative components. Patients with prominent cyclothymic profile got their diagnosis later in their life and had significantly higher mean scores on anger and hostility (non-motor aggressive behaviour) compared with patients with prominent hyperthymic profile. We included patients with different mood disorders, therefore the sample selection may influence temperamental and aggression profiles. We used self-report questionnaires which can elicit sociable desirable answers. Anger and hostility could represent stable personality characteristics of prominent cyclothymic profile that endure even in remission. It seems that distinct temperamental profile could serve as a good diagnostic and prognostic value for non-motor aspects of aggressive behaviour.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and neuroplasticity. Decreased blood levels of BDNF have been found during acute manic and depressive states. BDNF has been proposed as a biomarker in illness phases of mood disorders. No information is available regarding BDNF levels during the mixed states of bipolar disorder (BD). The aim of this study was to evaluate BDNF levels during mixed episodes of BD patients and compare them with those of healthy subjects and depressed patients. Plasma BDNF levels were measured by an ELISA assay in 18 patients with major depressive episode (MDE), 19 patients with mixed episode (ME) and 15 healthy subjects (HS). BDNF levels were significantly higher in HS, as compared with patients׳ samples (HS vs. MDE patients: p<001; HS vs. ME patients: p=.022). No significant differences were found between BDNF levels of ME and MDE patients. The severity of illness as assessed by CGI-S was significantly higher in ME than in MDE patients (p=.01). The small sample size may have weakened the power of statistical analyses. All patients received mood-stabilizing and antidepressant treatments which have been reported to influence peripheral BDNF levels. Our results are consistent with previous studies showing reduced BDNF during both manic and depressive episodes. This finding supports the role of BDNF as a state-marker of mood episodes, and may represent a contribution to a unitary approach model between unipolar and BDs, as well as to the manic-depressive spectrum model.

In comparing 101 psychotic patients subtyped by DSM-III criteria into paranoia, schizophrenia, schizoaffective, and affective disorders, we failed to distinguish them on the basis of delusional and hallucinatory experiences. These 'productive', 'positive' or 'irritative' symptoms--which the literature tends to link with temporolimbic dysfunction--did not appear specifically linked to schizophrenia. By contrast, 'negative' or 'deficit' symptoms--which the literature tends to relate to frontal lobe dysfunction--appeared more specific--especially for the disorganized subtype of schizophrenia. Although these data tend to support Bleulerian over Schneiderian conceptualization of schizophrenia, the heterogeneity of neuropsychological deficits implied in the negative symptom complexes limits the nosologic utility of the rubric of schizophrenia so defined.

We report on the utility of a new instrument to identify subtypes of major depressive episodes with special reference to pseudo-unipolar conditions. By incorporating reliable measures of depressive and hyperthymic temperamental characteristics in subtype definitions, we achieve the sharpest possible demarcation between unipolar and bipolar disorders. The new procedures also reveal that 1 out of 3 primary depressives in a consecutive series of 405 patients belong to the bipolar spectrum. Furthermore, among bipolars, bipolar II disorder (redefined as major depressions with hypomania or hyperthymic temperament) represents the most common variant. We discuss the nosologic, therapeutic, methodologic and theoretical implications of these considerations on the unipolar-bipolar dichotomy. Given that major depression emerges as the final common clinical expression of a heterogeneous group of disorders, it underscores the importance of focusing on temperament and course of illness in subclassification efforts such as attempted here.

We investigated the effect of co-morbid bipolar disorder and bulimia on temperamental dimensions measured by TEMPS-A, relative to "pure" bulimia and "pure" bipolar disorder, in female patients. The study was performed on 47 patients with bipolar disorder (BD) with a mean age of 36±10 years, 96 patients with bulimia or bulimic type of anorexia, mean age 26±9 years and 50 control healthy females (HC), mean age 29±6 years. Among bulimic patients, a group of 68 subjects with co-morbid bulimia with bipolarity (BD+B) was identified, based on positive score of the Mood Disorder Questionnaire (MDQ). The TEMPS-A questionnaire, 110 questions version, has been used, evaluating five temperament domains: depressive, cyclothymic, hyperthymic, irritable and anxious. Parametric analysis was performed for 4 groups (BD, "pure" bulimia (PB), BD+B and HC), with 28 subjects randomly chosen from each group, using analysis of variance and cluster analysis. All clinical groups significantly differed from control group by having higher scores of depressive, cyclothymic, irritable and anxious temperaments and lower of hyperthymic one. Among patients, significantly higher scores of cyclothymic and irritable temperaments were found in BD+B compared to both PB and BD. These differences were also reflected in cluster analysis, where two clusters were identified. Bipolarity in bulimic patients assessed only by the MDQ. These results show that co-morbid bulimia and bipolar disorder is characterized by extreme dimensions of both cyclothymic and irritable temperaments, significantly higher than each single diagnosis. Possible clinical implications of such fact are discussed.

Objective: To validate and clinically characterize mixed bipolar states derived from the concepts of Kraepelin and the Vienna School and defined as sustained instability of affective manifestations of opposite polarity — that usually fluctuate independently of one another — in the setting of marked emotional perplexity. Method: Our criteria for mixed states represent a modified “user-friendly” operationalization of these classical

ABSTRACT In an attempt to improve the classification of Bipolar II disorders, we have examined a consecutive series of 687 primary major depressives: 5.1% gave a past history of mania (Bipolar I), 13.7% met our operational criteria for hypomania (Bipolar II), and the remaining 81.2% were provisionally categorized as 'unipolar.' Although Bipolar II was in some respects intermediate between Bipolar I and Unipolar, gender, familial bipolar history, age at onset and course characteristics generally supported its closer kinship to bipolar illness. Seventy one of the unipolars (10.3% of the total series) further met our operational criteria for hyperthymic temperament (U-HT), leaving behind a purer unipolar group of 487 major depressives. With respect to the proportion having male gender and bipolar family history, U-HT was similar to Bipolar I and II, and all three differed significantly from pure unipolar; as for age at onset, number of episodes and related indices of course, BI and BII were similar, and U-HT was closer to pure unipolar. These findings suggest that major depressive episodes arising from a hyperthymic temperament (constituting 12.4% of the 'unipolar' universe by conventional definition) are 'genotypically' closer to Bipolar II defined by hypomania, and course-wise similar to other unipolars.

Epidemiological and clinical studies have reported the frequent co-occurrence of social phobia (SP) and alcohol use disorders. Patients with SP often use alcohol to cope with the social situations they fear, and to lessen anticipatory anxiety, behavioral inhibition, and phobic avoidance. We investigated whether the presence of lifetime comorbidity with alcohol abuse was associated with significant differences as regards demographic and clinical features, family history and pattern of comorbidity in a large clinical sample of SP outpatients. The sample comprised 153 outpatients who met DSM-III-R diagnostic criteria for SP. Demographic, family history and course characteristics were investigated by a semi-structured interview. Social phobic symptoms and the severity of the illness have been assessed by the Liebowitz Social Anxiety Scale (LSAS) and the Liebowitz Social Phobic Disorders Rating Scale, Severity (LSPDRS). Patients completed the Hopkins Symptom Checklist (HSCL 90). Thirty-four patients (22.2%) had a past or current history of alcohol abuse for at least 1 year. There were no significant differences between these patients and those without a history of alcohol abuse, as regards demographic features and lifetime comorbidity with major depression and other anxiety disorders. Bipolar disorder type II was found almost exclusively among patients with alcohol abuse, as well as family history for bipolar disorders. Retrospective study. Our data indicate a strong relationship between bipolar II disorder and alcohol abuse comorbidity in patients with SP. The socializing and disinhibiting effect that many social phobics report might be mediated by mood elation induced by alcohol. The presence of bipolar diathesis in patients presenting with social anxiety might explain their increased susceptibility to alcohol, as they might undertake alcohol abuse as an attempt to overcome social difficulties.