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Background and Aims:Psychiatric manifestations are very common in Connective Tissue Disorders as a manifestation of the disease process itself and not exclusively related to medication but are frequently overlooked by Psychiatrists and not taken into account by non-psychiatric Physicians.Methods:A brief summary of literature on the topic and presentation of clinical cases in which psychotic manic-like or depressive-like episodes are the first manifestation of Connective Tissue Disorders and how these cases evolve resembling Bipolar Disorder.Results:Atypical clinical presentations and other clinical signs and symptoms may lead to further diagnostic testing with positive Anti-nuclear and other auto-antibodies and the possible diagnosis of Connective Tissue Disorders.Conclusions:Psychotic manic-like and depressive-like episodes may be the initial presentation of Connective Tissue Disorders. Screening of ANA and anti-DNAds may eventually be warranted on a routine basis.