Lack of specific association between panicogenic properties of caffeine and HPA-axis activation. A placebo-controlled study of caffeine challenge in patients with panic disorder.

A subgroup of patients with Panic Disorder (PD) exhibits increased sensitivity to caffeine administration. However, the association between caffeine-induced panic attacks and post-caffeine hypothalamic-pituitary-adrenal (HPA)-axis activation in PD patients remains unclear. In a randomized, double-blind, cross-over experiment, 19 PD patients underwent a 400-mg caffeine-challenge and a placebo-challenge, both administered in the form of instant coffee. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at both baseline and post-challenge. No patient panicked after placebo-challenge, while nine patients (47.3%) panicked after caffeine-challenge. Placebo administration did not result in any significant change in hormones' plasma levels. Overall, sample's patients demonstrated significant increases in ACTH, cortisol, and DHEAS plasma levels after caffeine administration. However, post-caffeine panickers and non-panickers did not differ with respect to the magnitude of the increases. Our results indicate that in PD patients, caffeine-induced panic attacks are not specifically associated with HPA-axis activation, as this is reflected in post-caffeine increases in ACTH, cortisol and DHEAS plasma levels, suggesting that caffeine-induced panic attacks in PD patients are not specifically mediated by the biological processes underlying fear or stress. More generally, our results add to the evidence that HPA-axis activation is not a specific characteristic of panic.

Episodic Visual Learning/Memory and Attentional Flexibility in Patients With Major Depressive Disorder After Clinically Effective Electroconvulsive Therapy.

OBJECTIVES: This study is a follow-up of a previous one reporting that the neuropsychological profile of pharmacoresistant patients with major depressive disorder referred for electroconvulsive therapy (ECT, ECT group) contrasted with that of their pharmacorespondent counterparts (NECT group). The NECT group exhibited severe visuospatial memory and minor executive deficits; the ECT group presented the reverse pattern. In that same ECT group, the current follow-up study examined the effects of clinically effective ECT on both cognitive domains 2 months later. METHODS: Fifteen ECT patients were administered Hamilton Depression (HAMD-24), Hamilton Anxiety (HAMA), Mini-Mental State Examination Scales and 5 tests of Cambridge Neuropsychological Test Automated Battery at intake (pre-ECT), end of ECT course (post-ECT), and 2 months thereafter (follow-up). RESULTS: Electroconvulsive therapy was effective in relieving clinical depression. After a post-ECT decline, the patients exhibited significant improvement in both Cambridge Neuropsychological Test Automated Battery, paired associate learning, and Stockings of Cambridge. By contrast, their major pre-ECT deficit in intra/extradimensional set shifting remained virtually unaffected. CONCLUSIONS: Our findings suggest that attentional flexibility deficits may constitute a neuropsychological trait-like feature of pharmacoresistant, ECT-referred major depressive disorder patients. However, this deficit does not seem generalized, given patient improvement in episodic visual learning/memory and some indication of improvement in spatial planning after ECT.

Baseline heartbeat perception accuracy and short-term outcome of brief cognitive-behaviour therapy for panic disorder with agoraphobia.

BACKGROUND: Increased heartbeat perception accuracy (HBP-accuracy) may contribute to the pathogenesis of Panic Disorder (PD) without or with Agoraphobia (PDA). Extant research suggests that HBP-accuracy is a rather stable individual characteristic, moreover predictive of worse long-term outcome in PD/PDA patients. However, it remains still unexplored whether HBP-accuracy adversely affects patients' short-term outcome after structured cognitive behaviour therapy (CBT) for PD/PDA. AIM: To explore the potential association between HBP-accuracy and the short-term outcome of a structured brief-CBT for the acute treatment of PDA. METHOD: We assessed baseline HBP-accuracy using the "mental tracking" paradigm in 25 consecutive medication-free, CBT-naive PDA patients. Patients then underwent a structured, protocol-based, 8-session CBT by the same therapist. Outcome measures included the number of panic attacks during the past week, the Agoraphobic Cognitions Questionnaire (ACQ), and the Mobility Inventory-Alone subscale (MI-alone). RESULTS: No association emerged between baseline HBP-accuracy and posttreatment changes concerning number of panic attacks. Moreover, higher baseline HBP-accuracy was associated with significantly larger reductions in the scores of the ACQ and the MI-alone scales. CONCLUSION: Our results suggest that in PDA patients undergoing structured brief-CBT for the acute treatment of their symptoms, higher baseline HBP-accuracy is not associated with worse short-term outcome concerning panic attacks. Furthermore, higher baseline HBP-accuracy may be associated with enhanced therapeutic gains in agoraphobic cognitions and behaviours.

Psychotic major depression in older people: a systematic review.

OBJECTIVE: This study aimed to systematically review available evidence relevant to the following issues: (1) whether psychotic major depression (PMD) in older people differs in overall severity from non-PMD, besides the presence of psychotic symptoms; (2) whether it constitutes a distinct clinical entity from non-PMD; and (3) whether it differs from PMD in younger adults. DESIGN: A computerized MEDLINE, PsycINFO and the entire Cochrane Library search has been performed in June 2013 for prospective controlled studies investigating PMD features in older people. RESULTS: Thirty-five relevant studies were identified. PMD in older people compared with non-PMD has been shown to present with overall more severe depressive symptomatology, more psychomotor disturbance, more guilt feelings, more depressive episodes with psychosis, worse prognosis, more severe executive dysfunction associated with frontal lobe atrophy, and lower serum dopamine ß-hydroxylase activity. No differences in the efficacy of an antidepressant plus antipsychotic combination versus antidepressant monotherapy in the acute treatment as well as in the maintenance treatment were found. PMD in older patients is characterized by more somatic complaints and delusions of hypochondriacaland impending disaster content and by a lower comorbidity with anxiety disorders compared with PMD in younger adults. CONCLUSIONS: Psychotic major depression in older people is associated with higher severity in most clinically important key features than in non-PMD. However, available evidence is still insufficient for the conclusive elucidation of its nosological status. Finally, the differences between PMD in older and younger patients can be attributed to biological and psychosocial changes of old age.

Indoleamine 2,3-dioxygenase and immune changes under antidepressive treatment in major depression in females.

BACKGROUND/AIM: Indoleamine 2, 3-dioxygenase (IDO) induction has been suggested as a mechanism by which immune activation affects tryptophan metabolism and serotonin synthesis in major depressive disorder (MDD). We investigated IDO and changes in inflammatory mediators in patients with MDD undergoing effective treatment. PATIENTS AND METHODS: Forty female patients with MDD and 40 controls were recruited. Serum IDO was assessed by enzyme-linked immunosorbent assay (ELISA). We also determined tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), C-reactive protein (CRP) and serotonin concentrations. RESULTS: Patients' baseline concentrations of IDO and immune mediators were higher and serotonin concentrations were lower compared to controls. IDO and TNFα concentrations decreased under treatment and IDO changes were positively correlated with patient improvement. IFNγ and CRP concentrations remained unchanged. Serotonin concentration tended to increase. CONCLUSION: IDO might play an important role in the pathophysiology of MDD. Moreover, antidepressant therapy might reduce IDO production through an IFNγ-independent pathway. Finally, peripheral concentration of IDO assessed by ELISA might be a useful marker of MDD.

Self-rated and performance-based empathy in schizophrenia: the impact of cognitive deficits.

People may be much less empathic than they think they are. It is not clear whether patients with schizophrenia who have impaired empathic abilities also exhibit diminished ability to accurately appraise their own such skills. The present study aimed to examine: (a) the accuracy of self-appraisal of empathy and (b) the impact of specific cognitive functions on both self-rated and performance-based empathy in schizophrenia patients and healthy volunteers. Self-reported empathy and performance-based empathy were assessed in 52 chronic patients with schizophrenia and 45 matched healthy participants with the empathy quotient and the empathy score in the Faux Pas test, respectively. Neuropsychological functioning and symptom severity were also assessed. No significant correlations between self-reported and performance-based empathy scores were found in patients, whereas these correlations were significant and positive in the control group, with the exception of Faux Pas recognition. Cognitive deficits, specifically in processing speed and theory of mind, negatively affected performance-based but not self-rated empathy in schizophrenia. Patients with less negative and more positive symptoms and lower set shifting ability reported higher empathic abilities. Self-reported empathy and empathic abilities do not show a simple relationship. Our findings highlight a double deficit related to empathic responding in schizophrenia: diminished performance associated with cognitive deficits and inaccurate self-appraisal of empathic abilities.

The epistemological role of empathy in psychopathological diagnosis: a contemporary reassessment of Karl Jaspers' account.

INTRODUCTION: In his classic essay "The phenomenological approach to psychopathology", Karl Jaspers defended the irreducible reality of the "subjective" mental symptoms and stressed the pivotal role of empathy in their diagnostic assessment. However, Jaspers' account of the epistemological role of empathy in psychopathological diagnosis was far from clear: whereas at several places Jaspers claimed that empathy provides a direct access to patients' abnormal mental experiences, at other places he stressed that it did so only indirectly, through a whole battery of their observable clinical indicators. The aim of this paper is to reassess Jaspers' account of the epistemological role of empathy in psychopathological diagnosis. METHODS: I examine thoroughly Jaspers' assertions on in the role of empathy in the diagnosis of "subjective" symptoms. Moreover, I explicate briefly the epistemological status of psychopathological diagnostic examination with the aid of the distinction between direct and indirect observation. RESULTS: Diagnostic assessment of "subjective" mental symptoms involves necessarily indirect psychopathological observation. Jaspers' ambiguity is traced to his failure to distinguish clearly between direct and indirect psychopathological observation along with his excessive reliance on empathy. Relatedly, Jaspers' ambiguity is also traced to his conflation of the semantics with the epistemology of psychopathological concepts representing patients' "subjective" mental symptoms. These results apply also to contemporary phenomenological approaches to psychopathological diagnostic examination which maintain that patients' abnormal mental experiences are invariably expressed in their overt behavior. CONCLUSIONS: Jaspers was right in stressing that psychopathological concepts of subjective mental symptoms represent patients' genuine abnormal experiences irreducible to concepts representing their associated behavioral manifestations. Moreover, he was right in stressing the importance of the empathic 'second person' approach to patients' mental experiences. However, he failed to recognize unambiguously that the epistemological access to patients' mental symptoms, though enormously aided by empathy, remains mainly indirect and thus requires also a 'third person' approach to them. Overall then, clinical psychopathological examination requires both a 'second' and a 'third' person approach, as well as their judicious alternation during the diagnostic interview. Although focused on Jaspers' essay, my critical analysis is also highly relevant to contemporary psychopathological approaches aiming to overcome the serious limitations of currently prevailing systems of diagnostic criteria of mental disorders.

Cognitive effects of pregabalin in the treatment of long-term benzodiazepine-use and dependence.

OBJECTIVE: Long-term benzodiazepine (BDZ) use and dependence affect cognitive functioning adversely and partly irreversibly. Emerging evidence suggests that pregabalin (PGB) might be a safe and efficacious treatment of long-term BDZ use. The aim of the present study was to investigate the changes in several core cognitive functions after successful treatment of long-term BDZ use and dependence with PGB. METHODS: Fourteen patients with long-term BDZ use (mean duration >15 years) underwent neuropsychological assessment with the mini-mental state examination and four tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery before the initiation of PGB treatment and at a two months follow-up after the cessation of BDZs. Patients' CANTAB percentile score distributions were compared with normative CANTAB data. RESULTS: Patients improved on cognitive measures of global cognitive functioning, time orientation, psychomotor speed, and visuospatial memory and learning with strong effect sizes. By contrast, they failed to improve on measures of attentional flexibility. Despite their significant improvement, patients' scores on most tests remained still at the lower percentiles of CANTAB normative scores. CONCLUSIONS: Although preliminary, our findings suggest that successful treatment of long-term BDZ use with PGB is associated with a substantial, though only partial, recovery of BDZ-compromised neuropsychological functioning, at least at a 2-month follow-up.

Can cognitive deficits differentiate between schizophrenia with and without obsessive-compulsive symptoms?

BACKGROUND: The frequent occurrence of obsessive-compulsive symptoms (OCS) in the course of schizophrenia and their impact on the functional outcome of the illness underlie the suggestion that the presence of OCS represents a separate subtype of schizophrenia, with a distinct clinical presentation and prognosis and specific neurobiological characteristics. This study investigated whether the presence of OCS in schizophrenia is associated with worse cognitive functioning in the domains of processing speed, executive functions and visuospatial memory. We also explored whether the degree of impairment in any of these cognitive domains could predict group membership (i.e. Schizophrenia with OCS [Sch-OCS] and Schizophrenia without OCS) and if there was a relationship between cognitive functioning and severity of OCS within the Sch-OCS group. METHODS: Forty patients with schizophrenia, 20 with and 20 without OCS, individually matched for age, gender, years of education and severity of psychotic symptoms and 20 healthy controls underwent a comprehensive neuropsychological assessment. RESULTS: Only lower performance in processing speed discriminated patients with OCS from patients without OCS. Processing speed impairment not only classified patients in OCS or non-OCS group but was also independent of the severity of OCS symptoms. CONCLUSIONS: The notion of additive effects of both schizophrenia and OCD on the structural and functional integrity of the brain circuits that support cognitive functions warrants further investigation in longitudinal neuropsychological and neuroimaging studies with larger samples and sufficient variation in the severity of OCS.

Testosterone and dehydroepiandrosterone sulfate in female anxious and non-anxious major depression.

OBJECTIVES: Major Depression with severe anxiety has been proposed as a distinct clinical variant of Major Depressive Disorder (MDD). This proposal invites the investigation of the differential biological correlates of the anxious versus non-anxious MDD. One such research area might be their possible differential associations with androgens. METHODS: Plasma total testosterone and dehydroepiandrosterone were assessed in adequately matched female inpatients with anxious MDD, non-anxious MDD and normal controls. RESULTS: Androgen levels were significantly lower in both patient groups compared to those of controls. Moreover, they were significantly lower in anxious MDD patients compared to those of their non-anxious MDD counterparts. The limitations of this study were cross-sectional design of the study, the small sample size of the study sample and the outpatient status of the control group. In addition, free testosterone levels were not measured. CONCLUSIONS: Our findings indicate that female major depression is associated with lower androgen levels, a deficiency aggravated by the severity of their concomitant anxiety.

The relationship between insight and theory of mind in schizophrenia.

INTRODUCTION: It has been proposed that theory of mind (ToM) deficits underlying difficulties in taking the perspective of others may substantially contribute to insight impairment in schizophrenia. The present study aimed to explore the effect of ToM deficits on insight impairment independently of co-existent neurocognitive deficits and symptom severity in chronic schizophrenia. METHODS: Fifty-eight chronic patients with schizophrenia and 56 matched healthy participants were assessed with the Schedule for the Assessment of Insight (SAI-E) along with a series of ToM tasks and a comprehensive battery of neuropsychological measures. Symptoms were measured with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. RESULTS: ToM impairment explained a substantial proportion of variance in overall insight and its three major components: awareness of illness, relabelling of symptoms and treatment compliance. Moreover, the effect of ToM deficits on insight remained significant even after controlling for all neurocognitive factors and symptom ratings. Regression analysis showed that symptoms and cognitive deficits also contribute to impaired insight in schizophrenia. General intellectual ability was negatively associated with both overall insight and relabelling of symptoms. Executive functions were negatively associated with relabelling. CONCLUSION: Our findings confirm that ToM deficits negatively affect insight independently of neurocognitive deficits and symptom severity in chronic schizophrenia. The effect of ToM deficits on insight should be further examined in the broader context of the failures in metacognition and their relationships with insight impairment in schizophrenia.

Differential diagnosis of obsessive-compulsive symptoms from delusions in schizophrenia: A phenomenological approach.

Several studies suggest increased prevalence-rates of obsessive-compulsive symptoms (OCS) and even of obsessive-compulsive disorder (OCD) in patients with schizophrenic disorders. Moreover, it has been recently proposed the existence of a distinct diagnostic sub-group of schizo-obsessive disorder. However, the further investigation of the OCS or OCD-schizophrenia diagnostic comorbidity presupposes the accurate clinical differential diagnosis of obsessions and compulsions from delusions and repetitive delusional behaviours, respectively. In turn, this could be facilitated by a careful comparative examination of the phenomenological features of typical obsessions/compulsions and delusions/repetitive delusional behaviours, respectively. This was precisely the primary aim of the present investigation. Our examination included seven features of obsessions/delusions (source of origin and sense of ownership of the thought, conviction, consistency with one's belief-system, awareness of its inaccuracy, awareness of its symptomatic nature, resistance, and emotional impact) and five features of repetitive behaviours (aim of repetitive behaviours, awareness of their inappropriateness, awareness of their symptomatic nature, and their immediate effect on underlying thought, and their emotional impact). Several of these clinical features, if properly and empathically investigated, can help discriminate obsessions and compulsive rituals from delusions and delusional repetitive behaviours, respectively, in patients with schizophrenic disorders. We comment on the results of our examination as well as on those of another recent similar investigation. Moreover, we also address several still controversial issues, such as the nature of insight, the diagnostic status of poor insight in OCD, the conceptualization and differential diagnosis of compulsions from other categories of repetitive behaviours, as well as the diagnostic weight assigned to compulsions in contemporary psychiatric diagnostic systems. We stress the importance of the feature of mental reflexivity for understanding the nature of insight and the ambiguous diagnostic status of poor insight in OCD which may be either a marker of the chronicity of obsessions, or a marker of their delusionality. Furthermore, we criticize two major shortcomings of contemporary psychiatric diagnostic systems (DSM-IV, DSM-V, ICD-10) in their criteria or guidelines for the diagnosis of OCD or OCS: first, the diagnostic parity between obsessions and compulsions and, second, the inadequate conceptualization of compulsions. We argue that these shortcomings might artificially inflate the clinical prevalence of OC symptoms in the course of schizophrenic disorders. Still, contrary to a recent proposal, we do not exclude on purely a priori grounds the possibility of a concurrence of genuine obsessions along with delusions in patients with schizophrenia.

On the differential diagnosis of anxious from nonanxious major depression by means of the Hamilton Scales.

OBJECTIVE: Anxious major depressive disorder (A-MDD) is differentially diagnosed from nonanxious MDD (NA-MDD) as MDD with a cut-off score ≥ 7 on the HAM-D anxiety-somatization factor (ASF). We investigated whether additional HAM-D items discriminate A-MDD from NA-MDD. Moreover, we tested the validity of ASF criterion against HAM-A, gold standard of anxiety severity assessment. METHODS: 164 consecutive female middle-aged inpatients, diagnosed as A-MDD (n = 92) or NA-MDD (n = 72) by the normative HAM-A score for moderate-to-severe anxiety (≥ 25), were compared regarding 17-item HAM-D scores. The validity of ASF ≥ 7 criterion was assessed by receiver-operating characteristics (ROC) analysis. RESULTS: We found medium and large effect size differences between A-MDD and NA-MDD patients in only four out of the six ASF items, as well as in three further HAM-D items, namely, those of agitation, middle insomnia, and delayed insomnia. Furthermore, the ASF cut-off score ≥ 9 provided the optimal trade-off between sensitivity and specificity for the differential diagnosis between A-MDD and NA-MDD. CONCLUSION: Additional HAM-D items, beyond those of ASF, discriminate A-MDD from NA-MDD. The ASF ≥ 7 criterion inflates false positives. A cut-off point ≥ 9 provides the best trade-off between sensitivity and specificity of the ASF criterion, at least in female middle-aged inpatients.

Is insight in schizophrenia multidimensional? Internal structure and associations of the Greek version of the Schedule for the Assessment of Insight-Expanded.

Despite the general agreement that insight is a multidimensional phenomenon, the studies on the factorial structure of the scales for its assessment have yielded rather inconsistent results. The present study aimed to assess the internal structure of the Schedule for the Assessment of Insight (SAI-E). Seventy-two chronic patients with schizophrenia were assessed with SAI-E. Hierarchical cluster analysis and multidimensional scaling (MDS) were used to identify insight components and assess their inter-relationships. The associations of the extracted components with demographic, clinical and cognitive characteristics were also examined. The SAI-E demonstrated good psychometric properties. Three subscales of SAI-E were identified measuring awareness of illness, relabeling of symptoms, and treatment compliance. Moreover, the MDS disclosed two underlying dimensions--degree of 'specificity' and 'spontaneity'--within the insight construct. Treatment compliance was more strongly correlated with symptom relabeling than illness awareness. Excitement symptoms, global functioning and general intelligence were correlated with all the components of insight. Depressive symptoms were more strongly correlated with illness awareness. Impaired relabeling ability was linked to cognitive rigidity and greater severity of disorganization and positive symptoms. Education and severity of negative symptoms specifically affect treatment compliance. Our results support the hypothesis that insight is a multidimensional construct.

A magnetic resonance imaging study of hippocampal, amygdala and subgenual prefrontal cortex volumes in major depression subtypes: melancholic versus psychotic depression.

BACKGROUND: Volumetric studies examining brain structure in depression subtypes are limited and inconclusive. The aim of the current study was to compare the volumes of brain regions previously implicated in depression among patients with melancholic major depressive disorder (MDD), patients with psychotic MDD and normal controls. METHODS: Twenty two patients with melancholic MDD, 17 with psychotic MDD and 18 normal controls were included in the study. Hippocampal (HV), amygdala (AV), anterior (ASCV) and posterior (PSCV) subgenual cortex volumes were measured on magnetic resonance volumetric images. RESULTS: There were no volumetric differences between patients with melancholic and psychotic subgroups. We identified larger AVs and smaller left ASCVs in both patient groups compared to controls with medium to large effect sizes. Regression analysis revealed that AVs were predicted by the presence of depression, late depression-onset, insomnia and left hippocampal tail volume in patients, but not in controls. There were no differences in HVs, right ASCVs and PSCVs across the 3 groups. LIMITATIONS: Small sample size, a possible inclusion of paracingulate gyrus in ASCV and PSCV tracings, significant differences in education level and medication status are discussed as limitations. CONCLUSIONS: Diagnostically delineated melancholic and psychotic MDD patients do not differ in medial temporal and cingulate volumes. However, significant volumetric differences were detected between both patient-groups and controls.

On the nature of mental disorder: towards an objectivist account.

According to the predominant view within contemporary philosophy of psychiatry, mental disorders involve essentially personal and societal values, and thus, the concept of mental disorder cannot, even in principle, be elucidated in a thoroughly objective manner. Several arguments have been adduced in support of this impossibility thesis. My critical examination of two master arguments advanced to this effect by Derek Bolton and Jerome Wakefield, respectively, raises serious doubts about their soundness. Furthermore, I articulate an alternative, thoroughly objective, though in part normative, framework for the elucidation of the concept of mental disorder. The concepts of mental dysfunction and impairment of basic psychological capacities to satisfy one's basic needs are the building blocks of this framework. I provide an argument for the objective harmfulness of genuine mental disorders as patterns of mental dysfunctions with objectively negative biotic values, as well as a formally correct definition of the concept of mental disorder. Contrary to the received view, this objective framework allows for the possibility of genuine mental disorders due to adverse social conditions, as well as for quasi-universal mental disorders. I conclude that overall, the project of providing an objective account of the concept of mental disorder is far from impossible, and moreover, that it is, at least in principle, feasible.